qanastek/EMEA-V3 huggingface dataset:
Gingival bleeding, gastrointestinal haemorrhage, haemorrhoidal haemorrhage, peptic ulcer haemorrhage, oesophagitis, gastro-oesophageal reflux disease, colitis, caecitis, gastroduodenitis, aptyalism, proctitis, gastroenteritis, oesophageal pain, dysphagia, odynophagia, epigastric discomfort, aphthous stomatitis, cheilitis, glossodynia, gingivitis, lip ulceration, tongue ulceration, oral pain, toothache, sensitivity of teeth, oral hypoaesthesia, lip pain, coated tongue
Ħruġ ta ’ demm ġinġivali, emorraġija gastrointestinali, emorraġija tal- murliti, emorraġija ta ’ ulċera peptika, esofagite, mard tar- rifluss gastro- esofagali, kolite, infjammazzjoni tal- musrana l- għamja, gastroduwodenite, nuqqas/ assenza fis - sekrezzjoni tal- bżieq, proktite, gastroenterite, uġigħ esofagali, problemi biex tibla ’, odinofaġija, skonfort epigastriku, stomatite aphthous, infjammazzjoni tax- xufftejn, glossodinija, ġinġivite, ulċerazzjoni tax- xufftejn, ulċerazzjoni ta ’ l- ilsien, uġigħ fil - ħalq, uġigħ fis- snien, sensittività tas- snien, ipoestesija orali, uġigħ tax- xufftejn, ilsien miksi
Abnormal liver function tests, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin
Testijiet tal- funzjoni tal- fwied anormali, żieda fl- alanine aminotransferase, żieda fl - aspartate aminotransferase, żieda fil- bilirubina fid- demm
Erythema nodosum, urticaria, angioedema, eczema, erythrosis, erythematous rash, pruritic rash, papular rash, hyperkeratosis, skin fissures, acne, dermatitis acneiforme, lichen sclerosus, decubitus ulcer, pigmentation lip, prurigo, rosacea, photosensitivity reaction, seborroeic dermatitis, skin burning sensation, skin desquamation, skin discolouration † †
Raxx * Edema tal- wiċċ, ġilda xotta, ħakk *, eritema, follikulite, iperpigmentazzjoni tal - ġilda, raxx fil- ġilda kkaġunat minn xi infezzjoni minn virus, żieda fl- għaraq, għaraq matul il- lejl, alopeċja Eritema nodosum, urtikarja, anġjoedema †, ekżema, eritrosi, raxx eritematuż, raxx pruritiku, raxx papulari, iperkeratosi, qsim fil- ġilda, akne, dermatite acneiforme, lichen sclerosus, ulċera decubitus, pigmentazzjoni tax- xufftejn, prurigo, rosaċea, reazzjoni tas- sensittività għad- dawl, dermatite seborroeic, sensazzjoni ta ’ ħruq fil - ġilda, il- ġilda titqaxxar, tibdil fil- kulur tal- ġilda Is- sindrome ta ’ Stevens- Johnson †, nekrolisi epidermali tossika †
Musculoskeletal and connective tissue disorders Very Common:
Disturbi muskolu- skeletrali u tal- connective tissue Komuni ħafna:
Muscle cramp*, muscle weakness Common:
Komuni:
Steroid myopathy, myopathy, myalgia, arthralgia, back pain, bone pain, pain in limb, chest wall pain, peripheral swelling
Bugħawwieġ fil- muskoli *, dgħjufija fil- muskoli Mijopatija sterojdi, mijopatija, mijalġja, artralġja, uġigħ fid- dahar, uġigħ fl - għadam, uġigħ fir- riġlejn jew fid- dirgħajn, uġigħ fil- ħajt tas- sider, nefħa periferali
Osteonecrosis, muscle atrophy, amyotrophy, pain in foot, muscle spasms, musculoskeletal pain, night cramps, groin pain, pain in jaw, neck pain, spondylitis, joint stiffness, joint swelling, musculoskeletal stiffness, limb discomfort, toe deformities, local swelling
Osteonekrosi, atrofija tal- muskoli, amijotrofija, uġigħ fir- riġlejn, spażmi tal - muskoli, uġigħ muskoloskeletriku, bugħawwieġ matul il- lejl, uġigħ fil- groin, uġigħ fix- xedaq, uġigħ fl- għonq, spondilite, ebusija fil- ġogi, nefħa fil- ġogi, ebusija muskoloskeletrika, skonfort fir- riġlejn jew fid- dirgħajn, deformazzjonijiet fis - subgħajn tas- saqajn, nefħa lokali
disorders Renal failure, haematuria Acute renal failure, urinary frequency, renal tubular necrosis, cystitis, urinary retention, dysuria, acquired Fanconi Syndrome, urinary incontinence, polyuria, increased blood urea, increased blood creatinine, nocturia
Kollass renali, ematurja Kollass akut renali, frekwenza urinarja, nekrosi tubulari renali, ċistite, żamma ta ’ l - awrina, uġigħ u diffikultà biex tagħmel l- awrina, Sindrome ta ’ Fanconi miksub, inkontinenza urinarja, tagħmel ammont eċċessiv ta ’ awrina, żieda fl- urea fid - demm, żieda fil- kreatinina tad- demm, notturnja
11 Reproductive system and breast disorders Common:
Disturbi fis- sistema riproduttiva u fis- sider Komuni:
Erectile dysfunction, gynaecomastia, metrorrhagia, nipple pain
Disfunzjoni erettili, ginekomastija, tnixxija anormali tad- demm mill- ġuf, uġigħ f’ ras il- beżżula
Congenital, familial and genetic disorders Uncommon:
Disturbi konġenitali, familjali u ġenetiċi Mhux komuni:
Chromosome abnormality
Anormalità kromosomali
General disorders and administration site conditions Very Common:
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata Komuni ħafna:
Fatigue*, asthenia*, peripheral oedema Common:
Komuni:
Pyrexia, rigors, mucosal inflammation, oedema, lethargy, malaise Hyperpyrexia, chest pain, chest tightness, pain, difficulty in walking, abnormal gait, thirst, chest pressure sensation, feeling cold, feeling jittery, influenza-like illness, submandibular mass, fall, impaired healing
Għeja kbira *, astenja *, edema periferali Deni, tertir, infjammazzjoni mukuża, edema, letarġija, telqa Deni qawwi, uġigħ fis- sider, dwejjaq fis- sider, uġigħ, diffikultà meta timxi, timxi b’ mod anormali, għatx, sensazzjoni ta ’ pressjoni fis- sider, tħoss il- bard, tħossok nervuż/ a, mard bħal dak ta ’ l- influwenza, massa submandibulari, waqgħat, indeboliment fil- fejqan
Prolonged prothrombin time, prolonged activated partial thromboplastin time, increased International Normalised Ratio, increased blood alkaline phosphatase, increased blood lactate dehydrogenase, increased C-Reactive Protein, Cytomegalovirus antibody positive
Ħin imtawwal tal- prothrombin, ħin imtawwal tat- thromboplastin parzjali attivat, żieda fl - INR (International Normalised Ratio), żieda fl- alkaline phosphatase fid - demm, żieda fil- lactate dehydrogenase fid- demm, żieda fis- C- Reactive Protein, Cytomegalovirus antikorp pożittiv
Injury, poisoning and procedural complications Common:
12 Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura Komuni:
Contusion Wound complication
Korriment Kumplikazzjoni f’ xi ferita
Haemorrhagic disorders Haemorrhagic disorders are listed under several system organ classes:
Disturbi emorraġiċi Disturbi emorraġiċi huma elenkati taħt diversi klassijiet tal- organi tas- sistema:
Blood and lymphatic system disorders; nervous system disorders (intracranial haemorrhage); respiratory, thoracic and mediastinal disorders (epistaxis); gastrointestinal disorders (gingival bleeding, haemorrhoidal haemorrhage, rectal haemorrhage); renal and urinary disorders (haematuria); Injury, poisoning and procedural complications (contusion) and vascular disorders (ecchymosis).
Disturbi tad- demm u tas- sistema limfatika; disturbi fis- sistema nervuża (emorraġija intrakranjali); disturbi respiratorji, toraċiċi u medjastinali (tinfaraġ); disturbi gastro- intestinali (emorraġija ġinġivali, emorraġija tal - murliti, emorraġija tar- rektum, disturbi fil- kliewi u fis- sistema urinarja (ematurja); Korriment u avvelenament u komplikazzjonijiet ta 'xi proċedura (kontużjoni) u disturbi vaskulari (ekkimożi).
There is no specific experience in the management of lenalidomide over dose in multiple myeloma patients, although in dose-ranging studies some patients were exposed to up to 50 mg.
M’ hemm l- ebda esperjenza speċifika fl- immaniġġjar ta ’ doża eċċessiva ta ’ lenalidomide f’ pazjenti b’ mjeloma multipla, għalkemm fl- istudji dwar il- medda tad- doża, xi pazjenti kienu esposti sa 50 mg.
The dose limiting toxicity in these studies was essentially haematological.
It- tossiċità li tillimita d- doża f’ dawn l- istudji kienet essenzjalment ematoloġika.
In the event of overdose, supportive care is advised.
F’ każ ta ’ doża eċċessiva, kura ta ’ appoġġ hi rakkomandata.
Immunomodulating agent.
Sustanza immunomodulating.
The lenalidomide mechanism of action includes anti-neoplastic, anti-angiogenic, pro-erythropoietic, and immunomodulatory properties.
Il- mekkaniżmu ta ’ l- azzjoni ta ’ lenalidomide jinkludi proprjetajiet anti- neoplastiċi, anti- anġjoġeniċi, pro- eritropojetiċi, u immunomodulatorji.
Specifically, lenalidomide inhibits proliferation of certain haematopoietic tumour cells (including MM plasma tumour cells and those with deletions of chromosome 5), enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK T cells, inhibits angiogenesis by blocking the migration and adhesion of endothelial cells and the formation of microvessels, augments foetal haemoglobin production by CD34+ haematopoietic stem cells, and inhibits production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes.
Speċifikament, lenalidomide jinibixxi l- proliferazzjoni ta ’ ċerti ċelluli ematopojetiċi tat- tumur (li jinkludu celluli ta’ tumur MM plażma u dawk bi tħassir fi kromosoma 5), itejjeb l- immunità medjata taċ- ċelluli T u Natural Killer (NK) u jżid in- numru ta ’ ċelluli NKT, jinibixxi l- anġjoġenesi billi jimblokka l- migrazzjoni u l- adeżjoni ta ’ ċelluli endoteljali u l- formazzjoni ta ’ microvessels, iżid il- produzzjoni ta ’ l- emoglobina tal- fetu miċ- ċelluli staminali ematopojetiċi CD34+, u jinibixxi l- produzzjoni ta ’ cytokines pro- infjammatorji (eż., TNF- α u IL- 6) minn monocytes.
Clinical trials The efficacy and safety of lenalidomide were evaluated in two Phase III multi-centre, randomised, double-blind, placebo-controlled, parallel-group controlled studies (MM-009 and MM-010) of lenalidomide plus dexamethasone therapy versus dexamethasone alone in previously treated patients
Studji kliniċi L- effikaċja u s- sigurtà ta ’ lenalidomide kienu evalwati f’ żewġ studi ta ’ Fażi III, multi- centre, randomised, double- blind, ikkontrollati bil- plaċebo, ikkontrollati bil parallel- group (MM- 009 u MM - 010) b’ terapija ta ’ lenalidomide flimkien ma ’ dexamethasone kontra dexamethasone waħdu f’ pazjenti b’ mjeloma multipla, li qabel kienu kkurati.
Out of 353 patients in the MM-009 and MM-010 studies who received lenalidomide/dexamethasone, 45.6% were aged 65 or over.
Minn 353 pazjent fl- istudji MM- 009 u MM- 010 li rċievew lenalidomide/ dexamethasone, 45. 6% kellhom 65 sena jew iżjed.
Of the 704 patients evaluated in the MM-009 and MM-010 studies, 44.6% were aged 65 or over.
Mis- 704 pazjent evalwati fl- istudji MM- 009 u MM- 010, 44. 6% kellhom 65 sena jew iżjed.
In both studies, patients in the lenalidomide/dexamethasone (len/dex) group took 25 mg of lenalidomide orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28-day cycle.
Fiż- żewġ studji, il- pazjenti fil- grupp ta ’ lenalidomide/ dexamethasone (len/ dex) ħadu 25 mg ta ’ lenalidomide mill- ħalq darba kuljum f’ jiem 1 sa 21, u kapsula li taqbel tal- plaċebo darba kuljum f’ jiem 22 sa 28 f’ kull ċiklu ta ’ 28 jum.
Patients in the placebo/dexamethasone (placebo/dex) group took 1 placebo capsule on Days 1 to 28 of each 28-day cycle.
Il- pazjenti fil- grupp tal- plaċebo/ dexamethasone (plaċebo/ dex) ħadu kapsula 1 tal- plaċebo f’ jiem 1 sa 28 f’ kull ċiklu ta ’ 28 jum.
Patients in both treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy.
Il- pazjenti fiż- żewġ gruppi tal- kura ħadu 40 mg ta ’ dexamethasone mill- ħalq darba kuljum f’ jiem 1 sa 4, 9 sa 12, u 17 sa 20 f’ kull ċiklu ta ’ 28 jum għall- ewwel 4 ċikli tat- terapija.
The dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 of each 28-day cycle after the first 4 cycles of therapy.
Id- doża ta ’ dexamethasone tnaqqset għal 40 mg mill- ħalq darba kuljum f’ jiem 1 sa 4 f’ kull ċiklu ta ’ 28 jum wara l- ewwel 4 ċikli tat- terapija.
In both studies, treatment was to continue until disease progression.
Fiż- żewġ studji, il - kura kellha tkompli sakemm kien hemm progressjoni tal- marda.
In both studies, dose adjustments were allowed based on clinical and laboratory finding.
Fiż- żewġ studji, aġġustamenti tad - doża kienu permessi, ibbażati fuq is- sejbiet kliniċi u tal- laboratorju.
The primary efficacy endpoint in both studies was time to progression (TTP).
B’ kollox, 353 pazjenti kienu evalwati fl- istudju MM- 009; 177 fil- grupp ta ’ lenalidomide/ dexamethasone u 176 fil- grupp tal- plaċebo/ dexamethasone, u b’ kollox, 351 pazjent
In total, 353 patients were evaluated in the MM-009 study; 177 in the lenalidomide/dexamethasone group and 176 in the placebo/dexamethasone group and, in total, 351 patients were evaluated in the MM-010 study; 176 in the lenalidomide/dexamethasone group and 175 in the placebo/dexamethasone group.
13 kienu evalwati fi studju MM- 010; 176 fil- grupp ta ’ lenalidomide/ dexamethasone u 175 fil- grupp tal - plaċebo/ dexamethasone.
In both studies, the baseline demographic and disease-related characteristics were comparable between the lenalidomide/dexamethasone and placebo/dexamethasone groups.
Fiż- żewġ studji, il- linja bażi demografika u l- karatteristiċi relatati mal- marda kienu komparabbli bejn il- gruppi ta ’ lenalidomide/ dexamethasone u tal- plaċebo/ dexamethasone.
Both patient populations presented a median age of 63 years, with a comparable male to female ratio.
Iż- żewġ popolazzjonijiet ta ’ pazjenti kellhom medjan ta ’ età ta ’ 63 sena, bi proporzjon komparabbli bejn l- irġiel u n- nisa.
The ECOG performance status was comparable between both groups, as was the number and type of prior therapies.
L- istat tal- prestazzjoni ta ’ l- ECOG (Eastern Cooperative Oncology Group) kien komparabbli bejn iż- żewġ gruppi, kif kien ukoll in- numru u t- tip ta ’ terapiji ta ’ qabel.
Pre-planned interim analyses of both studies showed that lenalidomide/dexamethasone was statistically significantly superior (p < 0.00001) to dexamethasone alone for the primary efficacy endpoint, TTP.
L- analiżi interim ippjanata minn qabel taż- żewġ studji wrew li lenalidomide/ dexamethasone kien superjuri b’ mod statistikament sinifikanti (p < 0. 00001) meta mqabbel ma ’ dexamethasone waħdu, għar- riżultat aħħari ta ’ l- effikaċja primarja, TTP.
Complete response (CR) and overall response (OR) rates in the lenalidomide/dexamethasone arm were also significantly higher than the dexamethasone/placebo arm in both studies.
Ir- rati ta ’ rispons sħiħ (complete response - CR) u rispons totali (overall response - OR) fil- parti ta ’ l- istudju ta ’ lenalidomide/ dexamethasone kienu wkoll ogħla b’ mod sinifikanti mill- parti ta ’ l- istudju ta ’ dexamethasone/ plaċebo fiż- żewġ studji.
Results of these analyses subsequently led to an unblinding in both studies, in order to allow patients in the placebo/dexamethasone group to receive treatment with the lenalidomide/dexamethasone combination.
Ir - riżultati ta ’ dawn l- analiżi sussegwentement wasslu għal unblinding fiż- żewġ studji, biex jagħmilha possibbli li l- pazjenti fil- grupp tal- plaċebo/ dexamethasone li jirċievu l- kura bil- kumbinazzjoni b’ lenalidomide/ dexamethasone.
Table 1 summarises response rates based on the best response assessments for studies MM-009 and MM-010.
Tabella 1 turi fil- qosor ir- rati tar- rispons ibbażati fuq l- evalwazzjonijiet ta ’ l- aħjar risponsi għal studji MM- 009 u MM- 010.
In a pooled follow-up analysis of studies MM-009 and MM-010 (N = 704), the median TTP was 48.3 weeks (95% CI:
F’ analiżi follow- up kumbinat ta ’ studji MM- 009 u MM- 010 (n = 704), it- TTP medjan kien ta ’ 48. 3 ġimgħat (95% CI:
41.1, 60.1) in patients treated with lenalidomide/dexamethasone (n = 353) versus 20.1 weeks (95% CI:
41. 1, 60. 1) f’ pazjenti kkurati b ’ lenalidomide/ dexamethasone (n = 353) kontra 20. 1 ġimgħat (95% CI:
19.9, 20.7) in patients treated with placebo/dexamethasone (n = 351).
19. 9, 20. 7) f’ pazjenti kkurati bil- plaċebo/ dexamethasone (n = 351).
The median time of progression free survival (PFS) was 47.3 weeks (95% CI:
Il- medjan ta ’ żmien ta ’ sopravivenza mingħajr progressjoni (progression free survival - PFS) kien ta ’ 47. 3 ġimgħat (95% CI:
36.9, 58.4) in patients treated with lenalidomide/dexamethasone versus 20.1 weeks (95% CI:
36. 9, 58. 4) f’ pazjenti kkurati b’ lenalidomide/ dexamethasone kontra 20. 1 ġimgħat (95% CI:
18.1, 20.3) in patients treated with placebo/dexamethasone.
18. 1, 20. 3) f’ pazjenti kkurati bil- plaċebo/ dexamethasone.
The median duration of treatment was 28.1 weeks (min:
Il- medjan tat- tul ta ’ żmien tal- kura kien ta ’ 28. 1 ġimgħat (minimu:
0.1, max:
0. 1, massimu:
110.7).
110. 7).
Complete response (CR), partial response (PR) and overall response (OR) rates in the lenalidomide/dexamethasone arm were significantly higher than in the dexamethasone/placebo arm in both studies.
Ir- rati ta ’ rispons sħiħ (complete respons - CR), rispons parzjali (partial response - PR) u rispons totali (overall response - OR) fil- parti ta ’ l- istudju ta ’ lenalidomide/ dexamethasone kienu ogħla b’ mod sinifikanti minn dawk fil- parti ta ’ l - istudju ta ’ dexamethasone/ placebo fiż- żewġ studji.
The overall survival (OS) in the pooled studies at one year after the start of treatment was 82% in patients treated with lenalidomide/dexamethasone versus 75% in patients treated with placebo/dexamethasone, with a median follow-up duration of 98.0 weeks (min:
Is- sopravivenza totali (overall survival - OS) fl - istudji kumbinati sena wara l- bidu tal- kura kienet ta ’ 82% f’ pazjenti kkurati b’ lenalidomide/ dexamethasone kontra 75% f’ pazjenti kkurati bil- plaċebo/ dexamethasone, b’ medjan ta ’ tul ta ’ żmien tal- follow- up ta ’ 98. 0 ġimgħa (minimu:
0.3, max:
0. 3, massimu:
163.3).
163. 3).
Despite the fact that 170 out of the 351 patients randomised to placebo/dexamethasone received treatment with lenalidomide/dexamethasone after the studies were unblinded, the pooled analysis of OS demonstrated a statistically significant survival advantage for lenalidomide/dexamethasone relative to placebo/dexamethasone (hazard ratio = 0.75, 95% CI = [0.59, 0.95], p=0.015).
Minkejja l- fatt li 170 minn 351 pazjent li kienu randomised għall- plaċebo/ dexamethasone, irċievew il- kura b’ lenalidomide/ dexamethasone wara li l- istudji kienu unblinded, l- analiżi kumbinata ta ’ OS turi vantaġġ tas- sopravivenza li hu statistikament sinifikanti għal lenalidomide/ dexamethasone meta mqabbel mal- kura bil- plaċebo/ dexamethasone (proporzjon tal- periklu = 0. 75, 95% CI = [0. 59, 0. 95], p = 0. 015).
Table 1 summarises key efficacy results of the pooled follow-up analyses of studies MM-009 and MM-010.
Tabella 1 turi fil- qosor ir- riżultati ewlenin ta ’ l- effikaċja ta ’ l- analiżi follow- up kumbinata ta ’ studji MM- 009 u MM- 010.
Summary of Results of Efficacy Analyses as of Dates Studies Were Unblinded — Pooled Studies MM-009 and MM-010
Sommarju tar- Riżultati ta ’ l- Analiżi ta ’ l- Effikaċja sad- Dati ta ’ L- Istudji Kienu Unblinded — Studji kumbinati MM- 009 u MM- 010
Endpoint
Riżultat aħħari
placebo/dex
plaċebo/ dex
Hazard ratio/odds ratioa,
Proporzjon tal -
95% CI, p-value
periklu/ proporzjon ta ’ l - odds a, 95% CI, valur p
Median Time To Progression [weeks]
Time To Progression Medjan [ġimgħat
48.3
48. 3
0.35 [0.29, 0.43]
0. 35 [0. 29, 0. 43] p < 0. 001 b
[41.1, 60.1] [19.9, 20.7]
[19. 9, 20. 7]
p < 0.001 b
0. 18 [0. 13, 0. 25], p < 0. 001 c
Overall Response [n,%]
Rispons Totali [n,%]
214 (60.6)
214 (60. 6)
77 (21.9)
77 (21. 9)
0.18 [0.13, 0.25], p < 0.001 c
0. 12 [0. 05, 0. 26], p < 0. 001 c
Complete Response [n,%]
Rispons Sħiħ [n,%]
53 (15.0)
53 (15. 0)
7 (2.0)
7 (2. 0)
0.12 [0.05,0.26], p < 0.001 c
0. 30 [0. 21, 0. 42], p < 0. 001 c
Partial Response [n,%]
Rispons Parzjali [n,%]
161 (45.6)
161 (45. 6)
70 (19.9)
70 (19. 9)
Median Progression Free Survival [weeks]
Progression Free Survival Medjan [ġimgħat]
47.3
47. 3
0.38 [0.32, 0.46]
0. 38 [0. 32, 0. 46] p < 0. 001 b
[36.9, 58.4] [18.1, 20.3]
[18. 1, 20. 3]
p < 0.001 b
1- sena rata
1-year Overall Survival rate
ta ’ Sopravivenzal
0.75 [0.59, 0.95] p = 0.015 b
0. 75 [0. 59, 0. 95] p= 0. 015 b
Hazard ratio is for TTP, PFS and OS, odds ratio is for response rates.
Proporzjon tal- periklu huwa għal TTP, PFS u OS; proporzjon ta ’ l- odds huwa għar- rati tar- rispons.
A value below 1 in combination with a P value below 0.025 indicates superiority of len/dex over placebo/dex b:
Valur inqas minn 1 flimkien ma ’ valur ta ’ p inqas minn 0. 025 jindika superjorita’ ta ’ len/ dex fuq plaċebo/ dex. b:
One tailed continuity-corrected chi-square test
One tailed continuity- corrected chi- square test
Lenalidomide has an asymmetric carbon atom and can therefore ex ist as the optically active forms S(-) and R(+).
Lenalidomide għandu atomu asimmetriku tal- karbonju u għalhekk jista ’ jeżisti bħala l- forom attivi b’ mod ottiku S (-) u R( +).
Lenalidomide is produced as a racemic mixture.
Lenalidomide hu prodott bħala taħlita raċemika.
Lenalidomide is generally more soluble in organic solvents but exhibits the greatest solubility in 0.1N HCl buffer.
Lenalidomide ġeneralment jinħall iktar f’ solventi organiċi, iżda juri l- ikbar solubilità f’ soluzzjoni ta’ 0. 1N HCl.
Absorption Lenalidomide, in healthy volunteers, is rapidly absorbed following oral administration with maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose.
Assorbiment Lenalidomide, f’ voluntiera b’ saħħithom, jiġi assorbit malajr wara l- għoti mill- ħalq b’ konċentrazzjonijiet massimi fil- plażma li jseħħu bejn 0. 625 u 1. 5 sigħat wara d- doża.
Co-administration with food does not alter the extent of absorption.
L- għoti flimkien ma ’ l- ikel ma jibdilx l- ammont ta ’ assorbiment.
The maximum concentration (Cmax) and area-under-the- concentration time curve (AUC) increase proportionately with increases in dose.
Il- konċentrazzjoni massima (Cmax) u ż- żona taħt il- kurva konċentrazzjoni- ħin (area under the concentration time curve - AUC) jiżdiedu proporzjonalment ma ’ żiedet fid- doża.
Multiple dosing does not cause marked drug accumulation.
Dożaġġ multiplu ma jikkawżax akkumulazzjoni notevoli tal - mediċina.
In plasma, the relative exposures of the S- and R- enantiomers of lenalidomide are approximately 56% and 44%, respectively.
Fil- plażma, l- espożizzjonijiet ta’ l- enantiomers S - u R - ta’ lenalidomide huma madwar 56% u 44%, rispettivament.
Distribution In vitro (14C)-lenalidomide binding to plasma proteins was low with mean plasma protein binding at 22.7% and 29.2% in multiple myeloma patients and healthy volunteers, respectively.
Distribuzzjoni In vitro, it- twaħħil ta ’ (14C) - lenalidomide mal- proteini tal- plażma kien baxx b’ medja ta ’ twaħħil tal - proteini tal- plażma ta ’ 22. 7% u 29. 2% f’ pazjenti b’ mjeloma multipla u voluntiera b’ saħħithom rispettivament.
Metabolism and excretion In vitro studies indicate that lenalidomide has no inhibitory effect on CYP1 A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A.
Metaboliżmu u tneħħija Studji in vitro jindikaw li lenalidomide m’ għandu l- ebda effett inibitorju fuq CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, u CYP3A.
The contribution of renal excretion to total clearance in subjects with normal renal function was 65-85%.
Il- maġġoranza ta ’ lenalidomide jiġi eliminat mhux mibdul mit- tneħħija renali. Il- kontribut tat- tneħħija renali għat- tneħħija totali f’ pazjenti b’ funzjoni renali normali kienet 65- 85%.
The half-life of elimination has been observed to increase with dose, from approximately 3 hours at 5 mg up to approximately 9 hours at doses of 400 mg (the higher dose is believed to provide a better estimate of t½).
Il- half- life ta ’ l - eliminazzjoni kienet osservata li tiżdied mad- doża, minn madwar 3 sigħat f’ doża ta ’ 5 mg sa madwar 9 sigħat f’ dożi ta ’ 400 mg (id- doża l- għolja hi maħsuba li tipprovdi stima aħjar ta ’ t½).
Steady-state levels are achieved by Day 4.
Il- livelli fl- istat fiss jintlaħqu sa Jum 4.
Pharmacokinetics analyses in patients with impaired renal function indicate that as renal function decreases (< 50 ml/min), the total drug clearance decreases proportionally resulting in an increase in AUC.
L- analiżi tal- farmakokinetiċi f’ pazjenti b’ indeboliment fil- funzjoni renali jindikaw li hekk kif il - funzjoni renali tonqos (< 50 ml/ min), it- tneħħija totali tal- mediċina tonqos proporzjonalment, u
The half-life of lenalidomide increased from approximately 3.5 hours in subjects with creatinine clearance > 50 ml/min to more than 9 hours in subjects with reduced renal function < 50 ml/min.
Il- half- life ta ’ lenalidomide żdidet minn madwar 3. 5 sigħat f’ pazjenti bi tneħħija tal- kreatinina ta ’ > 50 ml/ min sa iktar minn 9 sigħat f’ pazjenti b’ funzjoni mnaqqsa renali ta ’ < 50 ml/ min.
However, renal impairment did not alter the oral absorption of lenalidomide.
Madankollu, l- indeboliment renali ma bidilx l- assorbiment orali ta ’ lenalidomide.
The Cmax was similar between healthy subjects and patients with renal impairment.
Is- Cmax kienet simili bejn pazjenti b’ saħħithom u pazjenti b’ indeboliment renali.
Recommended dose adjustments in patients with impaired renal function are described in section 4.2.
Aġġustamenti fid- doża rakkomandata f’ pazjenti b’ indeboliment fil- funzjoni renali huma deskritti f’ sezzjoni 4. 2.
Pharmacokinetic analyses based on multiple myeloma studies indicate that lenalidomide is rapidly absorbed at all dose levels, with maximum plasma concentrations occurring between 0.5 and 4.0 hours post-dose both on Days 1 and 28.
Analiżi farmakokinetiċi bbażati fuq studji dwar il- mjeloma multipla jindikaw li lenalidomide hu assorbit malajr fil- livelli kollha tad- doża, bil- konċentrazzjonijiet massimi tal- plażma li jseħħu bejn 0. 5 u 4. 0 sigħat wara li tingħata d- doża kemm f’ Jum 1 u 28.
The Cmax and AUC values increase proportionally with dose
Il- valuri tas- Cmax u ta ’ l- AUC jiżdiedu proporzjonalment mad- doża wara doża waħda jew dożi multipli, f’ pazjenti b’ mjeloma multipla.
Exposure in multiple myeloma patients is slightly higher based on Cmax and AUC values as compared to healthy male volunteers since the clearance/bioavailable fraction of a drug (CL/F) in multiple myeloma patients is lower (approximately 200 ml/min compared to 300 ml/min) than it is in healthy volunteers.
L - espożizzjoni f’ pazjenti b’ mjeloma multipla hi ftit ogħla, ibbażata fuq il- valuri Cmax u AUC kif imqabbla ma ’ voluntiera irġiel b’ saħħithom, għax il- porzjon tat- tneħħija/ bijodisponibbli tal- mediċina (CL/ F) f’ pazjenti b’ mjeloma multipla hu iktar baxx (madwar 200 ml/ min meta mqabbel ma ’ 300 ml/ min) milli hu f’ voluntiera b’ saħħithom.
This is consistent with the compromised renal function in the multiple myeloma patients, possibly as a consequence of their age (average patient age of 58 vs.
Dan hu konsistenti mal- funzjoni kompromessa renali f’ pazjenti b’ mjeloma multipla, possibbilment bħala konsegwenza ta ’ l- età tagħhom (età medja tal - pazjent ta ’ 58 sena vs.
29 for healthy volunteers) and their disease.
29 sena għal voluntiera b’ saħħithom) u l- marda tagħhom.
An embryofoetal development study has been conducted in monkeys administered lenalidomide at doses up to 4 mg/kg/day.
Sar studju dwar l- iżvilupp embrijofetali fuq xadini li ngħataw lenalidomide f’ dożi sa 4 mg/ kg/ kuljum.
Preliminary findings from this on-going study showed that lenalidomide produced malformations (short limbs, bent digits, wrist and/or tail, supernumerary or absent digits) in the offspring of female monkeys who received the drug during pregnancy.
Is- sejbiet preliminari ta ’ dan l- istudju li għadu għaddej urew li lenalidomide ipproduċa malformazzjonijiet (saqajn u dirgħajn qosra, subgħajn, polz u/ jew denb milwi, subgħajn żejda jew neqsin) fil- frieħ ta ’ xadini nisa li rċivew il- mediċina matul it- tqala.
Thalidomide produced similar types of malformations in the same study.
Thalidomide ipproduċa tipi ta ’ malformazzjonijiet simili fl- istess studju.
Lenalidomide has a potential for acute toxicity; minimum lethal doses after oral administration were > 2000 mg/kg/day in rodents.
Lenalidomide għandu l- potenzjal għal tossiċità akuta; id- dożi minimi letali wara l- għoti mill- ħalq kienu ta ’ > 2000 mg/ kg/ kuljum f’ annimali gerriema.
Repeated oral administration of 75, 150 and 300 mg/kg/day to rats for up to 26 weeks produced a reversible treatment-related increase in kidney pelvis mineralisation in all 3 doses, most notably in females.
L- għoti ripetut mill- ħalq ta ’ 75, 150 u 300 mg/ kg/ kuljum lil firien sa 26 ġimgħa, ipproduċa żieda riversibbli marbuta mal- kura fil - mineralizzazzjoni tal- pelvi u renali fit- 3 dożi kollha, l- aktar fin- nisa.
The no observed adverse effect level (NOAEL) was considered to be less than 75 mg/kg/day, and is approximately 25-fold greater than the human daily exposure based on AUC exposure.
In- no observed adverse effect level (NOAEL) kien ikkunsidrat li kien inqas minn 75 mg/ kg/ kuljum, u hu madwar 25 darba iktar mill- espożizzjoni ta ’ kuljum fil- bniedem ibbażata fuq l- AUC.
Repeated oral administration of 4 and 6 mg/kg/day to monkeys for up to 20 weeks produced mortality and significant toxicity (marked weight loss, reduced red and white blood cell and platelet counts, multiple organ haemorrhage, gastrointestinal tract inflammation, lymphoid, and bone marrow atrophy).
L- għoti ripetut mill- ħalq ta ’ 4 u 6 mg/ kg/ kuljum lix- xadini sa 20 ġimgħa, ipproduċa mortalità u tossiċità sinifikanti (telf notevoli tal - piż, tnaqqis fl- għadd taċ- ċelluli ħomor u bojod tad- demm u fl- għadd tal- plejtlits, emorraġiji multipli fl - organi, infjammazzjoni fl- apparat gastrointestinali, atrofija tal- limfi u ta ’ l- għadma tal- mudullun).
Repeated oral administration of 1 and 2 mg/kg/day to monkeys for up to 1 year produced reversible changes in bone marrow cellularity, a slight decrease in myeloid:erythroid cell ratio and thymic atrophy.
L - għoti ripetut mill- ħalq ta ’ 1 u 2 mg/ kg/ kuljum lix- xadini sa sena, ipproduċa tibdil riversibbli fiċ - ċellularità ta ’ l- għadma tal- mudullun, tnaqqis żgħir fil- proporzjon taċ- ċelluli mjelodi: eritrojdi u thymic atrophy.
Mild suppression of white blood cell count was observed at 1 mg/kg/day corresponding to approximately the same human dose based on AUC comparisons.
Trażżin ħafif ta ’ l- għadd taċ- ċelluli bojod tad- demm kien osservat b’ doża ta ’ 1 mg/ kg/ kuljum li tikkorispondi għal madwar l- istess doża umana bbażata fuq paraguni ta’ AUC.
In vitro (bacterial mutation, human lymphocytes, mouse lymphoma, Syrian Hamster Embryo cell transformation) and in vivo (rat micronucleus) mutagenicity studies revealed no drug related effects at either the gene or chromosomal level.
In vitro (mutazzjoni batterjali, limfoċiti umani, limfoma fil- ġrieden, trasformazzjoni taċ- ċelluli tas - Syrian Hamster Embryo) u in vivo (mikronukleu tal- firien) studji dwar il- mutaġeniċità dwar dawn il - fatturi ma żvelaw l- ebda effetti marbuta mal- mediċina, la fuq livell ta ’ ġeni u lanqas fuq livell kromosomali.
Carcinogenicity studies with lenalidomide have not been conducted.
Ma sarux studji dwar il- karċinoġeneċità b’ lenalidomide.
Developmental toxicity studies were previously conducted in rabbits.
Studji dwar it- tossiċità waqt l- iżvilupp saru qabel fil- fniek.
In these studies, rabbits were administered 3, 10 and 20 mg/kg/day orally.
F’ dawn l- istudji, il- fniek ngħataw 3, 10 u 20 mg/ kg/ kuljum oralment.
An absence of the intermediate lobe of the lung was observed at 10 and 20 mg/kg/day with dose dependence and displaced kidneys were observed at 20 mg/kg/day.
L- assenza tal- lobu intermedju tal- pulmun kienet osservata f’ dożi ta ’ 10 u 20 mg/ kg/ kuljum, b’ dipendenza fuq id- doża, u kliewi li ma kienux f’ posthom kienu osservati f’ doża ta ’ 20 mg/ kg/ kuljum.
Although it was observed at maternotoxic levels they may be attributable to a direct effect.
Għalkemm dan kien osservat f’ livelli maternotossiċi, huma jistgħu jkunu attribwibbli għal effett dirett.
Soft tissue and skeletal variations in the foetuses were also observed at 10 and 20 mg/kg/day.
Varjazzjonijiet fit- tessut artab u skeletriċi fil- feti kienu wkoll osservati f’ dożi ta ’ 10 u 20 mg/ kg/ kuljum.
Lactose, anhydrous Cellulose, microcrystalline Croscarmellose sodium Magnesium stearate
Lactose, anhydrous Cellulose, microcrystalline Croscarmellose sodium Magnesium stearate
Gelatin Titanium dioxide (E171)
Gelatin Titanium dioxide (E171)
Shellac Propylene glycol Black iron oxide (E172) Potassium hydroxide
Shellac Propylene glycol Black iron oxide (E172) Potassium hydroxide
Do not store above 25 C
Taħżinx f’ temperatura ’ l fuq minn 25ºC.
The capsules are provided in carton packs.
Il- kapsuli huma pprovduti f’ pakketti tal- kartun.
Each pack contains three Polyvinylchloride (PVC) / Polychlorotrifluoroethylene (PCTFE) / Aluminium foil blisters, each with seven capsules.
Kull pakkett fih tliet Polyvinylchloride (PVC) / Polychlorotrifluoroethylene (PCTFE) / Folji tal- fojl ta ’ l- aluminju, li kull waħda fiha seba ’ kapsuli.
This gives a total of 21 capsules per pack.
Dan jagħti total ta ’ 21 kapsula f’ kull pakkett.
Unused medicinal product should be returned to the pharmacist.
Il- prodott mediċinali mhux użat għandu jittieħed lura għand l- ispiżjar.
Celgene Europe Limited Riverside House Riverside Walk Windsor Berkshire SL4 1NA United Kingdom
Celgene Europe Limited Riverside House Riverside Walk Windsor Berkshire SL4 1NA Ir- Renju Unit
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu/.
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu.
Revlimid 10 mg hard capsules
Revlimid 10 mg kapsuli iebsin
Each capsule contains 10 mg of lenalidomide.
Kull kapsula fiha 10 mg ta ’ lenalidomide.
Each capsule contains 294 mg of anhydrous lactose.
Kull kapsula fiha 294 mg ta ’ anhydrous lactose.
Blue-green/pale yellow capsules marked “REV 10 mg”.
Kapsuli blu- ħodor/ isfar ċar immarkati “ REV 10 mg ”.
Lenalidomide treatment must not be started if the Absolute Neutrophil Counts (ANC) < 1.0 x 109/l, and/or platelet counts < 75 x 109/l or, dependent on bone marrow infiltration by plasma cells, platelet counts < 30 x 109/l.
Il- kura b’ lenalidomide m’ għandhiex tinbeda jekk l- Għadd Assolut tan- Newtrofili (Absolute Neutrophil Counts - ANC) ikun ta ’ < 1. 0 x 109/ l u/ jew l- għadd tal- plejtlits ikun ta ’ < 75 x 109/ l jew, dipendenti fuq l- infiltrazzjoni ta ’ l- għadma tal- mudullun miċ- ċelluli tal- plażma, l- għadd tal- plejtlits ikun ta ’ < 30 x 109/ l.
Recommended dose adjustments during treatment and restart of treatment Dose adjustments, as summarised below, are recommended to manage grade 3 or 4 neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide.
19 Aġġustamenti rakkomandati tad- doża matul il- kura u l- bidu mill- ġdid tal- kura Aġġustamenti tad- doża, murija fil- qosor hawn taħt, huma rakkomandati biex timmaniġġja newtropenja jew tromboċitopenja ta ’ grad 3 jew 4, jew xi tossiċità oħra ta ’ grad 3 jew 4 li tkun iġġudikata li tkun marbuta ma ’ lenalidomide.
17 • Dose reduction steps
• Passi biex tnaqqas id- doża
No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out.
20 effikaċja ma kienet osservata bejn dawn il- pazjenti u l- pazjenti li kienu iżgħar, iżda l- predispożizzjoni ikbar f’ individwi li għandhom iktar żmien ma tistax tiġi eskluża.
18 No dose adjustments are required for patients with mild renal impairment.
L- ebda aġġustamenti fid- doża m’ huma meħtieġa għal pazjenti b’ indeboliment ħafif renali.
1 5 mg every other day**
15 mg kull jumejn **
Counselling For women of childbearing potential, lenalidomide is contraindicated unless all of the following are met: • She understands the expected teratogenic risk to the unborn child • She understands the need for effective contraception, without interruption, 4 weeks before starting treatment, throughout the entire duration of treatment, and 4 weeks after the end of treatment • Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective contraception
21 • Operazzjoni salpingo- oophorectomy bilaterali, jew isterektomija li jkunu saru fil- passat • Ġenotip XY, sindromu ta ’ Turner, aġenesi ta ’ l- utru. * Amenorrea wara terapija tal- kanċer ma teskludix li l- mara jista ’ jkollha tfal.
19 • She should be capable of complying with effective contraceptive measures • She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy • She understands the need to commence the treatment as soon as lenalidomide is dispensed following a negative pregnancy test • She understands the need and accepts to undergo pregnancy testing every 4 weeks except in case of confirmed tubal sterilisation • She acknowledges that she understands the hazards and necessary precautions associated with the use of lenalidomide.
Pariri Għal nisa li jista ’ jkollhom tfal, lenalidomide hu kontra- indikat ħlief jekk dawn li ġejjin kollha jkunu sodisfatti: • Hi tifhem ir- riskju teratoġeniku mistenni lit- tarbija mhix imwielda • Hi tifhem il- ħtieġa għal kontraċezzjoni effettiva mingħajr interruzzjoni, 4 ġimgħat qabel tibda l - kura, matul il- perijodu kollu tal- kura, u 4 ġimgħat wara t- tmiem tal- kura • Anki jekk mara li jista ’ jkollha tfal ikollha l- amenorrea, trid issegwi l- pariri kollha dwar kontraċezzjoni effettiva • Hi għandha tkun kapaċi li tkun konformi b’ miżuri ta ’ kontraċezzjoni effettiva • Hi nfurmata u tifhem il- konsegwenzi potenzjali tat- tqala u l- ħtieġa li tieħu parir malajr jekk hemm riskju ta ’ tqala • Hi tifhem il- ħtieġa li tibda l- kura malli tingħata lenalidomide wara test tat- tqala negattiv • Hi tifhem il- ħtieġa u taċċetta li tagħmel test tat- tqala kull 4 ġimgħat minbarra f’ każ ta ’ sterilizzazzjoni tat- tubi kkonfermata • Tirrikonoxxi li tifhem il- perikli u l- prekawzjonijiet meħtieġa marbuta ma ’ l- użu ta ’ lenalidomide.
20 requirement includes women of childbearing potential who practice absolute and continuous abstinence.
Din il- ħtieġa tinkludi nisa li jista ’ jkollhom tfal li jipprattikaw astinenza sesswali assoluta u kontinwa.
Additional precautions Patients should be instructed never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of treatment.
Prekawzjonijiet addizzjonali Il- pazjenti għandhom jingħataw struzzjonijiet biex qatt ma jagħtu dan il- prodott mediċinali lil xi persuna oħra u biex jieħdu lura kwalunkwe kapsuli mhux użati lill- ispiżjar tagħhom fit- tmiem tal- kura.
Concomitant administration of erythropoietic agents or previous history of DVT may also increase thrombotic risk in these patients.
23 eritropojetiċi jew storja medika ta ’ DVT fil- passat, jistgħu wkoll iżidu r- riskju trombotiku f’ dawn il - pazjenti.
The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment.
24 tumur kbir jew estensiv qabel il- kura.
22 to reduced efficacy of drugs, including hormonal contraceptives, is not expected if lenalidomide is administered alone.
Għalhekk, l- induzzjoni li twassal għal tnaqqis fl- effikaċja tal- mediċini, li jinkludu kontraċettivi ormonali, mhijiex mistennija jekk lenalidomide jingħata waħdu.
Warfarin Co-administration of multiple doses of 10 mg of lenalidomide had no effect on the single dose pharmacokinetics of R- and S- warfarin.
Warfarin L- għoti flimkien ta ’ dożi multipli ta ’ 10 mg ta ’ lenalidomide ma kellu l- ebda effett fuq il - farmakokinetiċi ta ’ dożi waħidhom ta ’ R - u S - warfarin.
Lenalidomide induced in monkeys malformations similar to those described with thalidomide (see section 5.3).
25 Lenalidomide ipproduċa malformazzjonijiet fix- xadini simili għal dawk deskritti b’ thalidomide (ara sezzjoni 5. 3).
23 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa
24 Blood and lymphatic system disorders Very Common:
Disturbi tad- demm u tas- sistema limfatika Komuni ħafna:
Nervous system disorders Common:
27 Disturbi fis- sistema nervuża Komuni:
26 Reproductive system and breast disorders Common:
Disturbi fis- sistema riproduttiva u fis- sider Komuni:
Injury, poisoning and procedural complications Common:
29 Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura Komuni:
There is no specific experience in the management of lenalidomide overdose in multiple myeloma patients, although in dose-ranging studies some patients were exposed to up to 50 mg.
M’ hemm l- ebda esperjenza speċifika fl- immaniġġjar ta ’ doża eċċessiva ta ’ lenalidomide f’ pazjenti b’ mjeloma multipla, għalkemm fl- istudji dwar il- medda tad- doża, xi pazjenti kienu esposti sa 50 mg.
27 lenalidomide plus dexamethasone therapy versus dexamethasone alone in previously treated patients with multiple myeloma.
Studji kliniċi L- effikaċja u s- sigurtà ta ’ lenalidomide kienu evalwati f’ żewġ studi ta ’ Fażi III, multi- centre, randomised, double- blind, ikkontrollati bil- plaċebo, ikkontrollati bil parallel- group (MM- 009 u MM - 010) b’ terapija ta ’ lenalidomide flimkien ma ’ dexamethasone kontra dexamethasone waħdu f’ pazjenti b’ mjeloma multipla, li qabel kienu kkurati.
In total, 353 patients were evaluated in the MM-009 study; 177 in the lenalidomide/dexamethasone group and 176 in the placebo/dexamethasone group and, in total, 351 patients were evaluated in the MM-010 study; 176 in the lenalidomide/dexamethasone group and 175 in the placebo/dexamethasone group.
30 kienu evalwati fi studju MM- 010; 176 fil- grupp ta ’ lenalidomide/ dexamethasone u 175 fil- grupp tal - plaċebo/ dexamethasone.
(N=353)
= 353)
One-tailed log rank test c:
One- tailed log rank test c:
Metabolism and excretion In vitro studies indicate that lenalidomide has no inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A.
Metaboliżmu u tneħħija Studji in vitro jindikaw li lenalidomide m’ għandu l- ebda effett inibitorju fuq CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, u CYP3A.
Developmental toxicity studies were previously conducted in rabbits.
F’ dawn l- istudji, il- fniek ngħataw 3, 10 u 20 mg/ kg/ kuljum oralment.
In these studies, rabbits were administered 3, 10 and 20 mg/kg/day orally.An absence of the intermediate lobe of the lung was observed at 10 and 20 mg/kg/day with dose dependence and displaced kidneys were observed at 20 mg/kg/day.
L- assenza tal- lobu intermedju tal- pulmun kienet osservata f’ dożi ta ’ 10 u 20 mg/ kg/ kuljum, b’ dipendenza fuq id- doża, u kliewi li ma kienux f’ posthom kienu osservati f’ doża ta ’ 20 mg/ kg/ kuljum.
Soft tissue and skeletal variations in the foetuses were also observed at 10 and 20 mg/kg/day..
Varjazzjonijiet fit- tessut artab u skeletriċi fil- feti kienu wkoll osservati f’ dożi ta ’ 10 u 20 mg/ kg/ kuljum.
Gelatin Titanium dioxide (E171) Indigo carmine (E132) Yellow iron oxide (E172)
Gelatin Titanium dioxide (E171) Indigo carmine (E132) Yellow iron oxide (E172)
Shellac Propylene glycol
Linka ta ’ l- istampar:
Black iron oxide (E172) Potassium hydroxide
Shellac Propylene glycol Black iron oxide (E172) Potassium hydroxide
Revlimid 15 mg hard capsules
Revlimid 15 mg kapsuli iebsin
Each capsule contains 15 mg of lenalidomide.
Kull kapsula fiha 15 mg ta ’ lenalidomide.
Each capsule contains 289 mg of anhydrous lactose.
Kull kapsula fiha 289 mg ta ’ anhydrous lactose.
Pale blue/white capsules marked “REV 15 mg”.
Kapsuli blu ċari/ bojod immarkati “ REV 15 mg ”.
Recommended dose adjustments during treatment and restart of treatment Dose adjustments, as summarised below, are recommended to manage grade 3 or 4 neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide.
36 Aġġustamenti rakkomandati tad- doża matul il- kura u l- bidu mill- ġdid tal- kura Aġġustamenti tad- doża, murija fil- qosor hawn taħt, huma rakkomandati biex timmaniġġja newtropenja jew tromboċitopenja ta ’ grad 3 jew 4, jew xi tossiċità oħra ta ’ grad 3 jew 4 li tkun iġġudikata li tkun marbuta ma ’ lenalidomide.
32 • Dose reduction steps
• Passi biex tnaqqas id- doża
No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out.
37 effikaċja ma kienet osservata bejn dawn il- pazjenti u l- pazjenti li kienu iżgħar, iżda l- predispożizzjoni ikbar f’ individwi li għandhom iktar żmien ma tistax tiġi eskluża.
33 No dose adjustments are required for patients with mild renal impairment.
L- ebda aġġustamenti fid- doża m’ huma meħtieġa għal pazjenti b’ indeboliment ħafif renali.
Counselling For women of childbearing potential, lenalidomide is contraindicated unless all of the following are met: • She understands the expected teratogenic risk to the unborn child • She understands the need for effective contraception, without interruption, 4 weeks before starting treatment, throughout the entire duration of treatment, and 4 weeks after the end of treatment • Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective contraception
38 • Operazzjoni salpingo- oophorectomy bilaterali, jew isterektomija li jkunu saru fil- passat • Ġenotip XY, sindromu ta ’ Turner, aġenesi ta ’ l- utru. * Amenorrea wara terapija tal- kanċer ma teskludix li l- mara jista ’ jkollha tfal.
34 • She should be capable of complying with effective contraceptive measures • She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy • She understands the need to commence the treatment as soon as lenalidomide is dispensed following a negative pregnancy test • She understands the need and accepts to undergo pregnancy testing every 4 weeks except in case of confirmed tubal sterilisation • She acknowledges that she understands the hazards and necessary precautions associated with the use of lenalidomide.
Pariri Għal nisa li jista ’ jkollhom tfal, lenalidomide hu kontra- indikat ħlief jekk dawn li ġejjin kollha jkunu sodisfatti: • Hi tifhem ir- riskju teratoġeniku mistenni lit- tarbija mhix imwielda • Hi tifhem il- ħtieġa għal kontraċezzjoni effettiva mingħajr interruzzjoni, 4 ġimgħat qabel tibda l - kura, matul il- perijodu kollu tal- kura, u 4 ġimgħat wara t- tmiem tal- kura • Anki jekk mara li jista ’ jkollha tfal ikollha l- amenorrea, trid issegwi l- pariri kollha dwar kontraċezzjoni effettiva • Hi għandha tkun kapaċi li tkun konformi b’ miżuri ta ’ kontraċezzjoni effettiva • Hi nfurmata u tifhem il- konsegwenzi potenzjali tat- tqala u l- ħtieġa li tieħu parir malajr jekk hemm riskju ta ’ tqala • Hi tifhem il- ħtieġa li tibda l- kura malli tingħata lenalidomide wara test tat- tqala negattiv • Hi tifhem il- ħtieġa u taċċetta li tagħmel test tat- tqala kull 4 ġimgħat minbarra f’ każ ta ’ sterilizzazzjoni tat- tubi kkonfermata • Tirrikonoxxi li tifhem il- perikli u l- prekawzjonijiet meħtieġa marbuta ma ’ l- użu ta ’ lenalidomide.
If not est ablished on effective contraception, the patient must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated.
Jekk ma tkunx stabbilita fuq kontraċezzjoni effettiva, il - pazjenta għandha tiġi riferuta lil professjonist fil- qasam tas- saħħa li jkun imħarreġ kif suppost, għal parir fuq il- kontraċezzjoni biex il- kontraċezzjoni tkun tista ’ tinbeda.
35 requirement includes women of childbearing potential who practice absolute and continuous abstinence.
Din il- ħtieġa tinkludi nisa li jista ’ jkollhom tfal li jipprattikaw astinenza sesswali assoluta u kontinwa.
Concomitant administration of erythropoietic agents or previous history of DVT may also increase thrombotic risk in these patients.
40 eritropojetiċi jew storja medika ta ’ DVT fil- passat, jistgħu wkoll iżidu r- riskju trombotiku f’ dawn il - pazjenti.
The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment.
41 tumur kbir jew estensiv qabel il- kura.
37 to reduced efficacy of drugs, including hormonal contraceptives, is not expected if lenalidomide is administered alone.
Għalhekk, l- induzzjoni li twassal għal tnaqqis fl- effikaċja tal- mediċini, li jinkludu kontraċettivi ormonali, mhijiex mistennija jekk lenalidomide jingħata waħdu.
Lenalidomide induced in monkeys malformations similar to those described with thalidomide (see section 5.3).
42 Lenalidomide ipproduċa malformazzjonijiet fix- xadini simili għal dawk deskritti b’ thalidomide (ara sezzjoni 5. 3).
38 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa
39 Blood and lymphatic system disorders Very Common:
Disturbi tad- demm u tas- sistema limfatika Komuni ħafna:
Nervous system disorders Common:
44 Disturbi fis- sistema nervuża Komuni: