qanastek/EMEA-V3 huggingface dataset:
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
27 Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.
The
Tagħrif dwar iż- żmien meta l- istat newroloġiku mar għall- agħar iffavorixxa TMZ fuq procarbazine, kif għamel it- tagħrif dwar iż- żmien meta l- istatut ta ’ prestazzjoni mar għall- agħar (tnaqqis għal KPS ta ’ < 70 jew tnaqqis b’ mill- inqas 30 punt).
27 median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Iż- żminijiet medjani għall- progressjoni f’ dawn l- endpoints varja minn 0. 7 sa 2. 1 xhur aktar għal TMZ milli għal procarbazine (log rank p = < 0. 01 sa 0. 03).
Recurrent anaplastic astrocytoma
Astroċitoma anaplastika rikurrenti
28 Special populations
Popolazzjonijiet speċjali
Analysis of population-based pharmacokinetics of TMZ revealed that plasma TMZ clearance was independent of age, renal function or tobacco use.
Analiżi tal- farmakokinetika ta ’ TMZ ibbażata fuq il- popolazzjoni wrew li t- tneħħija mill- plażma ta ’ TMZ kienet indipendenti mill- età, funzjoni tal- kliewi jew l- użu tat- tabakk.
Dose- related reductions in leukocytes and platelets appear to be sensitive indicators of toxicity.
It- tnaqqis fil- lewkoċiti u fil- plejtlets relatat mad- doża jidher li 29 huwa indikatur sensittiv tat- tossiċità.
Capsule shell: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron oxide (E 172)
Qoxra tal- kapsula: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron oxide (E 172),
Bottle presentation
L- għamla tal- flixkun
Sachet presentation
L- għamla tal- qratas
Bottle presentation
30 L- għamla tal- flixkun
Sachet presentation
Għamla tal- qratas
Sachets are composed of linear low density polyethylene (innermost layer), aluminium and polyethylene terephthalate.
Il- qrata huma magħmula minn polyethylene linjari ta ’ densità baxxa (saff ta ’ ġewwa nett), aluminium u polyethylene terephthalate.
Each sachet contains 1 hard capsule and is dispensed in a cardboard carton.
Kull qartas fih kapsula iebsa 1 u jingħata f’ kartuna tal- kardbord.
The carton contains 5 or 20 hard capsules, individually sealed in sachets.
Il- kartuna fiha 5 jew 20 kapsula iebsa, issiġillati b’ mod individwali fi qratas.
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) 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 /
Temodal 100 mg hard capsules
Kapsuli iebsin Temodal 100 mg
Each hard capsule contains 100 mg temozolomide.
Kull kapsula iebsa fiha 100 mg ta ’ temozolomide.
Each hard capsule contains 175.7 mg of anhydrous lactose.
Kull kapsla iebsa fiha 175. 7 mg anhydrous lactose.
The hard capsules have an opaque white body, an opaque pink cap, and are imprinted with black ink.
Il- kapsuli iebsin għandhom naħa bajda opaka, b’ għatu opak roża, u ttimbrati b’ inka sewda.
The body is imprinted with "100 mg", the Schering-Plough logo and two stripes.
In- naħa l- oħra ttimbrata b ’ ” 100 mg ”, il- logo ta ’ Schering- Plough u żewġ strippi.
No dose reductionsare recommended, but delay or discontinuation of TMZ administration should be decided weekly according to haematological and non -haematological toxicity criteria.
Mhux rakkomandat li jitnaqsu d- dożi, iżda l- għotja ta ’ TMZ għandha tkun rimandata jew imwaqqfa fuq deċiżjoni li tittieħed kull ġimgħa skond kriterji ta ’ tossiċità ħematoloġika u dik mhux ħematoloġika.
≥ 0.5 and < 1.5 x 10 /l
≥ 0. 5 u < 1. 5 x 10 / l < 10 x 109/ l
≥ 10 and < 100 x 109/l
≥ 10 u < 100 x 109/ l
33 Table 3.
33 Tabella 3.
Based on the ph armacokinetic properties of TMZ, it is unlikely that dose reductions are required in patients with severe hepatic impairment or any degree of renalimpairment.
Ibbażat fuq il - karatteristiċi farmakokinetika ta ’ TMZ, tnaqqis fid- doża x’ aktarx li ma jkunx meħtieġ f’ pazjenti b’ indeboliment epatiku serju jew kwalunkwe grad ta ’ indeboliment renali.
Hypersensitivity to the active substanceor to any of the excipients.
34 Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
34 Severe myelosuppression (see section 4.4).
Majelosoppressjoni severa (ara sezzjoni 4. 4).
35 Male patients
35 Pazjenti anzjani jidhru li huma f' riskju akbar li jkollhom newtropenja u tromboċitopenja, meta mqabbla ma ’ pazjenti iżgħar.
Women of childbearing potential should be advised to use effective contraception to avoid pregnancy while they are receiving TMZ. pregnancy while they are receiving TMZ.
Nisa li potenzjalment jista ’ jkollhom it- tfal għandhom jingħataw il- parir biex jużaw metodu ta ’ kontraċezzjoni effettiv biex jevitaw li joħorġu tqal waqt li jkunu qed jirċievu TMZ.
It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.
36 Mhux magħruf jekk TMZ joħroġx mal- ħalib tal- mara; għalhekk, it- treddigħ għandu jitwaqqaf waqt il - kura b’ TMZ.
In patients treated with TMZ, whe ther used in combination with RT or as monotherapy following RT for newly-diagnosed glioblastoma multiforme, or as monotherapy in patients with recurrent or progressive glioma, the reported very common adverse reactions were similar: nausea, vomiting, constipation, anorexia, headache and fatigue.
F’ pazjenti ikkurati b’ TMZ, kemm kombinat ma ’ RT, jew bħala monoterapija wara RT għal glioblastoma multiforme li tkun għada kif ġiet dijanjostikata, jew bħala monoterapija f’ pazjenti b’ glijoma rikurrenti jew progressiva, l- effetti avversi komuni ħafna rappurtati kienu simili: tqallih, rimettar, stitikezza, anoressija, uġigħ ta ’ ras u għejja.
Uncommon:
37 Mhux komuni:
Common:
38 Komuni:
38 Common:
Komuni:
Uncommon:
39 Mhux komuni:
40 Gender
Sess
In the event of an overdose, haematological evaluation is needed.
41 infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
41 TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija tas- salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
The hazard ratio (H R) for overall survival was 1.59 (9 5% CI for HR=1 .33 -1.91) with a log-rank p < 0.0001 in favour of the TMZ arm.
Il- proporzjon tal- periklu (HR) għas- sopravivenza ġenerali kienet ta ’ 1. 59 (95% CI għal HR=1. 33 - 1. 91) b’ log rank p < 0. 0001 favur il- fergħa ta ’ TMZ.
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
42 Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.
42 median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Iż- żminijiet medjani għall- progressjoni f’ dawn l- endpoints varja minn 0. 7 sa 2. 1 xhur aktar għal TMZ milli għal procarbazine (log rank p = < 0. 01 sa 0. 03).
Oral TMZ has been studied in paediatric patients (age 3-18 years) with recurrent brainstem glioma or recurrent high grade astrocytoma, in a regimen admin istered daily for 5 days every 28 days.
TMZ orali kien studjat f’ pazjenti pedjatriċi (età 3- 18- il sena) bi brainstem glioma rikurrenti jew astroċitoma rikurrenti ta ’ grad għoli, f’ kors mogħti kuljum għal 5 ijiem kull 28 jum.
43 Special populations
Popolazzjonijiet speċjali
Dose- related reductions in leukocytes and platelets appear to be sensitive indicators of toxicity.
It- tnaqqis fil- lewkoċiti u fil- plejtlets relatat mad- doża jidher li 44 huwa indikatur sensittiv tat- tossiċità.
Capsule shell: gelatin, titanium dioxide (E 171), sodium lauril sulfate, red iron oxide (E172).
Qoxra tal- kapsula: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron oxide (E 172),
Bottle presentation
45 L- għamla tal- flixkun
Temodal 140 mg hard capsules
Kapsuli iebsin Temodal 140 mg
Each hard capsule contains 140 mg temozolomide.
Kull kapsula iebsa fiha 140 mg ta ’ temozolomide.
Each hard capsule contains 246 mg of anhydrous lactose.
Kull kapsla iebsa fiha 246 mg anhydrous lactose.
Hard capsule The hard capsules have an opaque white body, a blue cap, and are imprinted with black ink.
Il- kapsuli iebsin għandhom naħa bajda opaka, b’ għatu opak ċelesti, u ttimbrati b’ inka sewda.
The body is imprinted with "140 mg", the Schering-Plough logo and two stripes.
In- naħa l- oħra ttimbrata b ’ ” 140 mg ”, il- logo ta ’ Schering- Plough u żewġ strippi.
- adult patients with newly-diagnosed gliobl astoma multiforme concomitantly with radiotherapy
- pazjenti adulti b’ glioblastoma multiforme li tkun għada kemm ġiet dijanjostikata flimkien ma ’
- thrombocyte count ≥ 100 x 109/l
47 għadd tat- tromboċiti ≥ 100 x 109/ l
47 During treatment a complete blood count should be obtained weekly.
Waqt il- kura, l- għadd komplet tad- demm għandu jinkiseb kull ġimgħa.
48 Table 3.
48 Tabella 3.
In patients previously untreated with chemotherapy, TMZ is administered orally at a dose of 200 mg/m2 once daily for the first 5 days followed by a 2 3 day treatment interruption (total of 28 days).
F’ pazjenti li qabel ma kinux ikkurati bil- kimoterapija, TMZ jittieħed mill- ħalq f’ doża ta ’ 200 mg/ m2 darba kuljum għall- ewwel 5 tijiem, segwiti minn 23 jum ta ’ waqfien mil- kura (total ta ’ 28 jum).
Hypersensitivity to the active substanceor to any of the excipients.
49 Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
49 Severe myelosuppression (see section 4.4).
Majelosoppressjoni severa (ara sezzjoni 4. 4).
50 Male patients
50 Pazjenti anzjani jidhru li huma f' riskju akbar li jkollhom newtropenja u tromboċitopenja, meta mqabbla ma ’ pazjenti iżgħar.
It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.
51 Mhux magħruf jekk TMZ joħroġx mal- ħalib tal- mara; għalhekk, it- treddigħ għandu jitwaqqaf waqt il - kura b’ TMZ.
51 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Uncommon:
52 Mhux komuni:
52 Psychiatric disorders Common:
Komuni:
Common:
53 Komuni:
53 Common:
Komuni:
Uncommon:
54 Mhux komuni:
55 Gender
Sess
In the event of an overdose, haematological evaluation is needed.
56 infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
56 TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija tas- salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
The estimated probability of surviving 2 years or more (26% vs 10%) is higher for the R T + TMZ arm.
Il- probabilità stmata li jkun hemm sopravivenza ta ’ sentejn jew aktar (26% vs 10%) hija ogħla għall- fergħa ta ’ RT + TMZ.
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
57 Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.
57 median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Iż- żminijiet medjani għall- progressjoni f’ dawn l- endpoints varja minn 0. 7 sa 2. 1 xhur aktar għal TMZ milli għal procarbazine (log rank p = < 0. 01 sa 0. 03).
58 Special populations
Popolazzjonijiet speċjali
Dose- related reductions in leukocytes and platelets appear to be sensitive indicators of toxicity.
It- tnaqqis fil- lewkoċiti u fil- plejtlets relatat mad- doża jidher li 59 huwa indikatur sensittiv tat- tossiċità.
Capsule shell: gelatin, titanium dioxide (E 171), sodium lauril sulfate, indigo carmine (E 132),
Qoxra tal- kapsula: gelatin, titanium dioxide (E 171), sodium lauril sulfate, indigo carmine (E 132),
Bottle presentation
60 L- għamla tal- flixkun
Temodal 180 mg hard capsules
Kapsuli iebsin Temodal 180 mg
Each hard capsule contains 180 mg temozolomide.
Kull kapsula iebsa fiha 180 mg ta ’ temozolomide.
Each hard capsule contains 316.3 mg of anhydrous lactose.
Kull kapsla iebsa fiha 316. 3 mg anhydrous lactose.
Hard capsule The hard capsules have an opaque white body, an opaque orange cap, and are imprinted with black ink.
Il- kapsuli iebsin għandhom naħa bajda opaka, b’ għatu opak oranġjo, u ttimbrati b’ inka sewda.
The body is imprinted with "180 mg", the Schering-Plough logo and two stripes.
In- naħa l- oħra ttimbrata b ’ ” 180 mg ”, il- logo ta ’ Schering- Plough u żewġ strippi.
No dose reductionsare recommended, but delay or discontinuation of TMZ administration should be decided weekly according to haematological and non -haematological toxicity criteria.
Mhux irrakkomandat li jitnaqqsu d- dożi, iżda l- għotja ta ’ TMZ għandha tkun rimandata jew imwaqqfa fuq deċiżjoni li tittieħed kull ġimgħa skond kriterji ta ’ tossiċità ħematoloġika u dik mhux ħematoloġika.
62 During treatment a complete blood count should be obtained weekly.
Waqt il- kura, l- għadd komplet tad- demm għandu jinkiseb kull ġimgħa.
63 Table 3.
63 Tabella 3.
Hypersensitivity to the active substanceor to any of the excipients.
64 Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
64 Severe myelosuppression (see section 4.4).
Majelosoppressjoni severa (ara sezzjoni 4. 4).
65 Male patients
65 Pazjenti anzjani jidhru li huma f' riskju akbar li jkollhom newtropenja u tromboċitopenja, meta mqabbla ma ’ pazjenti iżgħar.
It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.
66 Mhux magħruf jekk TMZ joħroġx mal- ħalib tal- mara; għalhekk, it- treddigħ għandu jitwaqqaf waqt il - kura b’ TMZ.
66 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Uncommon:
67 Mhux komuni:
67 Psychiatric disorders Common:
Komuni:
Common:
68 Komuni:
68 Common:
Komuni:
Uncommon:
69 Mhux komuni:
70 Gender
Sess
In the event of an overdose, haematological evaluation is needed.
71 infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
L01 A X03
Aġenti antineoplastiċi – alkylating agents oħra, kodiċi ATC L01A X03
71 TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija tas- salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
72 Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.
In p atients with prior chemotherapy a benefit was indicated in those with a KPS ≥ 80.
F’ pazjenti li ngħataw il- kemoterapija qabel, il - benefiċċju kien indikat f’ dawk b’ KPS ta ’ ≥80.
72 median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Iż- żminijiet medjani għall- progressjoni f’ dawn l- endpoints varja minn 0. 7 sa 2. 1 xhur aktar għal TMZ milli għal procarbazine (log rank p = < 0. 01 sa 0. 03).
73 Special populations
Popolazzjonijiet speċjali
Dose- related reductions in leukocytes and platelets appear to be sensitive indicators of toxicity.
It- tnaqqis fil- lewkoċiti u fil- plejtlets relatat mad- doża jidher li 74 huwa indikatur sensittiv tat- tossiċità.
Capsule shell: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron oxide (E 172), red iron oxide (E 172)
Qoxra tal- kapsula: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron oxide (E 172), red iron oxide (E 172)
Printing ink: shellac, propylene glycol, purified water, ammonium hydroxide, potassium hydroxide,
Stampar: shellac, propylene glycol, ilma purifikat, ammonium hydroxide, potassium hydroxide, black iron oxide (E 172).
Keep the bottle tightly closed.
Taħżinx f’ temperatura ’ l fuq minn 30°C Aħżen fil- flixkun oriġinali sabiex tilqa mill- umdità.
Sachet presentation
Żomm il- flixkun magħluq sewwa.
Do not store above 30 °C.
L- għamla tal- qratas
Bottle presentation
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih 75 L- għamla tal- flixkun
Temodal 250 mg hard capsules
Kapsuli iebsin Temodal 250 mg
Each hard capsule contains 250 mg temozolomide.
Kull kapsula iebsa fiha 250 mg ta ’ temozolomide.
Each hard capsule contains 154.3 mg of anhydrous lactose.
Kull kapsla iebsa fiha 154. 3 mg anhydrous lactose.
The hard capsules have an opaque white body and cap and are imprinted with black ink.
Il- kapsuli iebsin għandhom iż- żewġ naħat bojod u opaki u huma ittimbrati b’ inka sewda.
The body is imprinted with "250 mg", the Schering -Plough logo and two stripes.
In- naħa l- oħra ttimbrata b ’ ” 250 mg ”, il- logo ta ’ Schering- Plough u żewġ strippi.
Adult patients with newly -diagnosed glioblastoma multiforme
Pazjenti adulti li jkunu għadhom kif ġew dijanjostikati b’ glioblastoma multiforme
78 Table 3.
78 Tabella 3.
Hypersensitivity to the active substanceor to any of the excipients.
79 Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
79 Severe myelosuppression (see section 4.4).
Majelosoppressjoni severa (ara sezzjoni 4. 4).
80 Male patients
80 Pazjenti anzjani jidhru li huma f' riskju akbar li jkollhom newtropenja u tromboċitopenja, meta mqabbla ma ’ pazjenti iżgħar.
It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.
81 Mhux magħruf jekk TMZ joħroġx mal- ħalib tal- mara; għalhekk, it- treddigħ għandu jitwaqqaf waqt il - kura b’ TMZ.
81 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Uncommon:
82 Mhux komuni:
82 Psychiatric disorders Common:
Komuni:
Common:
83 Komuni:
83 Common:
Komuni:
Uncommon:
84 Mhux komuni:
85 Gender
Sess
In the event of an overdose, haematological evaluation is needed.
86 infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
Temozolomide is a triazene, which undergoes rapid chemical conversion at physiologic pH to the active monomethyl triazenoimidazole carboxamide (MTIC).
Temozolomide huwa triazene, li fil- pH fiżjoloġiku jinbidel malajr f’ sustanza attiva (MTIC).
Cytotoxic lesions that develop subsequently are thought to involve aberrant repair of the methyl adduct.
Ġrieħi ċitotossiċi li jiżviluppaw sussegwentement huma maħsuba li jinvolvu t- tiswija anormali tal - methyl adduct.
86 TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija tas- salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
87 Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.
In both trials, the primary endpoint was progression-free survival (PFS) defined by MRI scans or neurological worsening.
Fiż- żewġ provi, l- endpoint primarju kien is- sopravivenza mingħajr progressjoni (PFS) kif definita minn skans ta ’ MRI jew mis- sistema newroloġika li tmur għall- agħar.
In the non- comparative trial, the PFS at 6 months was 19%, the median progression-free survival was 2.1 months, and the median overall survival 5.4 months.
Fl- istudju mhux komparattiv, il - PFS wara 6 xhur kien ta ’ 19%, is- sopravivenza mingħajr progressjoni medjana kienet ta ’ 2. 1. xhur, u l- medjan tas- sopravivenza totali kien ta ’ 5. 4 xhur.
87 median times to progression in these endpoints ranged from 0.7 to 2.1 months longer for TMZ than for procarbazine (log rank p = < 0.01 to 0.03).
Iż- żminijiet medjani għall- progressjoni f’ dawn l- endpoints varja minn 0. 7 sa 2. 1 xhur aktar għal TMZ milli għal procarbazine (log rank p = < 0. 01 sa 0. 03).
88 Special populations
Popolazzjonijiet speċjali
Dose- related reductions in leukocytes and platelets appear to be sensitive indicators of toxicity.
It- tnaqqis fil- lewkoċiti u fil- plejtlets relatat mad- doża jidher li 89 huwa indikatur sensittiv tat- tossiċità.
Capsule shell: gelatin, titanium dioxide (E 171), sodium lauril sulfate
Qoxra tal- kapsula: gelatin, titanium dioxide (E 171), sodium lauril sulfate,
Type I amber glass bottles with polypropylene child-resistant closures containing 5 -or 20 hard capsules.
L- għamla tal- flixkun 90 Fliexken tal- ħġieġ kannella jagħti fl- oranġjo tat- Tip I b’ għeluq ta ’ polypropylene li huma reżistenti għat- tfal u li fihom 5- jew 20 kapsula iebsa.
Temodal 2.5 mg/ml powder for solution for infusion
Temodal 2. 5 mg/ ml trab għal soluzzjoni għall- infużjoni
Each vial contains 100 mg of temozolomide.
Kull kunjett fih 100 mg ta ’ temozolomide.
After reconstitution, 1 ml solution for infusion contains 2.5 mg temozolomide.
Wara li jkun rikostitwit, ml 1 ta ’ soluzzjoni għall- infużjoni jkun fih 2. 5 mg temozolomide.
Each vial contains 2.4 mmol sodium.
Kull kunjett fih 2. 4 mmol sodium.
White powder.
Trab abjad.
Temodal 2.5 mg/ ml is indicated for the treatment of:
Temodal 2. 5 mg/ ml huwa indikat għal- kura ta ’:
as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.
glioblastoma multiforme jew astroċitoma anaplastika, li jerġgħu jirkadu jew ikollhom avvanz tal- marda wara li tkun ingħatat terapija standard.
Temodal 2.5 mg/ml should only be prescribed by physicians experienced in the oncological treatment of brain tumours.
Temodal 2. 5 mg/ ml għandu jinkiteb biss minn tobba b’ esperjenza fil- kura onkoloġika ta ’ tumuri tal - moħħ.
Temodal 2.5 mg/ml is administered in combination with focal radiotherapy (concomitant phase) followed by up to 6 cycles of temozolomide (TMZ) monotherapy (monotherapy phase).
Temodal 2. 5 mg/ ml jingħata kumbinat ma ’ radjuterapija fokali (fażi konkomitanti) segwit b’ mhux aktar minn 6 ċikli b’ monoterapiji ta ’ temozolomide (TMZ) (fażi ta ’ monoterapija).
TMZ is administered at a dose of 75 mg/m2 daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions).
Fażi meta jingħataw flimkien TMZ jingħata b’ doża ta ’ 75 mg/ m2 kuljum għal 42 jum flimkien ma ’ radjuterapija fokali (60 GY mogħtija fi 30 frazzjonijiet).
No dose reductions are recommended, but delay or discontinuation of TMZ administration should be decided weekly according to haematological and non- haematological toxicity criteria.
Mhux rakkomandat li jitnaqsu d- dożi, iżda l- għotja ta ’ TMZ għandha tkun rimandata jew imwaqqfa fuq deċiżjoni li tittieħed kull ġimgħa skond kriterji ta ’ tossiċità ħematoloġika u dik mhux ħematoloġika.
TMZ administration can be continued throughout the 42 day concomitant period (up to 49 days) if all of the following conditions are met:
L- għotja ta ’ TMZ tista ’ titkompla fil- perijodu ta ’ 42 jum meta jkunu qed jingħataw flimkien (sa 49 jum) jekk il- kundizzjonijiet kollha li ġejjin ikunu jgħoddu: għadd assolut tan- newtrofili (ANC) ≥ 1. 5 x 109/ l • għadd tat- tromboċiti ≥ 100 x 109/ l •
- common toxicity criteria (CTC) non-haematological toxicity ≤ Grade 1 (except for alopecia,
92 • Kriterji Tossiċi Komuni (CTC), tossiċità ħematoloġika ≤ Grad 1 (ħlief għal alopeċja, tqallih u rimettar).
9
Għadd assolut tan- newtrofili
≥ 0.5 and < 1.5 x 10 /l
≥ 0. 5 u < 1. 5 x 109/ l
< 0.5 x 109/l
< 10 x 109/ l
Thrombocyte count CTC non-h aematological toxicity
Għadd tat- tromboċiti Tossiċità mhux ħematoloġika CTC (ħlief għal alopeċja, tqallih,
Four weeks after completing the TMZ + RT concomitant phase, TMZ is administered for up to 6 cycles of monotherapy treatment.
Fażi ta ’ Monoterapija Erba ’ ġimgħat wara li ntemmet il- fażi konkomitanti ta ’ TMZ + RT, TMZ ikompli jingħata sa ’ 6 ċikli ta ’ kura b’ monoterapija.
Dose in Cycle 1 (monotherapy) is 150 mg/m2 once daily for 5 days followed by 23 days without treatment.
Id- doża f’ Ċiklu 1 (monoterapija) hija 150 mg/ m2 darba kuljum għal 5 tijiem segwit b’ 23 jum mingħajr kura.
Dose reductions and discontinuations during the monotherapy phase should be applied according to Tables 2 and 3.
It- tnaqqis u t- twaqqif tad- dożi waqt il- fażi ta ’ monoterapija għandhom isiru skond Tabelli 2 u 3.
TMZ dose (mg/m2/day)
Doża TMZ (mg/ m2/ jum)
93 Table 3.
93 Tabella 3.
TMZ dose reduction or discontinuation during monotherapy treatment
Tnaqqis jew twaqqif tad- doża ta ’ TMZ waqt kura b’ monoterapija
Reduce TMZ by 1 dose levela
Naqqas TMZ b’ livell ta ’ doża 1a
dose level -1 (100 mg/m2) still results in unacceptable toxicity the same Grade 3 non-haematological toxicity (except for alopecia, nausea, vomiting) recurs after dose reduction.
L- istess tossiċità mhux ħematoloġika ta ’ Grade 3 (ħlief għal alopeċja, tqallih, rimettar) terġa tiġri wara tnaqqis fid- doża.
In patients previously untreated with chemotherapy, TMZ is administered at a dose of 200 mg/m2 once daily for the first 5 days followed by a 23 day treatment interruption (total of 28 days).
F’ pazjenti li qabel ma kinux ikkurati bil- kimoterapija, TMZ jittieħed f’ doża ta ’ 200 mg/ m2 darba kuljum għall- ewwel 5 ijiem, segwit minn 23 jum ta ’ waqfien mill- kura (total ta ’ 28 jum).
In patients previously treated with chemotherapy, the initial dose is 150 mg/m2 once daily, to be increased in the second cycle to 200 mg/m2 once daily, for 5 days if there is no haematological toxicity (see section 4.4)
F’ pazjenti li qabel kienu kkurati bil- kimoterapija, id- doża tal- bidu hija 150 mg/ m2 darba kuljum, li tkun miżjuda fit- tieni ċiklu għal 200 mg/ m2 darba kuljum, għal 5 ijiem jekk ma jkunx hemm tossiċità ħematoloġika (ara sezzjoni 4. 4)
In patients 3 years of age or older, TMZ is only to be used in recurrent or progressive malignant glioma.
F’ pazjenti ta ’ 3 snin jew akbar, TMZ jintuża biss f’ każ ta ’ glijoma malinna rikurrenti jew progressiva.
Experience in older children is very limited (see sections 4.4 and 5.1).
Esperjenza fi tfal akbar hija limitata ħafna (ara sezzjonijiet 4. 4 u 5. 1).
Patients with hepatic or renal impairment
Pazjenti b’ funzjoni epatika jew renali indebolita
The pharmacokinetics of TMZ were comparable in patients with normal hepatic function and in those with mild or moderate hepatic impairment.
Il- farmakokinetika ta ’ TMZ kienet kumparabbli f' pazjenti b’ funzjoni epatika normali u f’ dawk b’ indeboliment epatiku ħafif jew moderat.
No data are available on the administration of TMZ in patients with severe hepatic impairment (Child’s Class C) or with renal impairment.
M’ hemmx dejta disponibbli dwar l- għoti ta ’ TMZ f’ pazjenti b’ indeboliment epatiku sever (Child’ s Class C) jew b’ indeboliment renali.
Based on the pharmacokinetic properties of TMZ, it is unlikely that dose reductions are required in patients with severe hepatic impairment or any degree of renal impairment.
Ibbażat fuq il - karatteristiċi farmakokinetiċi ta ’ TMZ, mhux probabbli li jkunu meħtieġa tnaqqis fid- dożi f’ pazjenti b’ indeboliment epatiku sever jew kwalunkwe grad ta ’ indeboliment renali.
Based on a population pharmacokinetic analysis in patients 19-78 years of age, clearance of TMZ is not affected by age.
Ibbażat fuq analiżi farmakokinetika tal- popolazzjoni f’ pazjenti bejn 19- 78 sena, it- tneħħija ta ’ TMZ mhijiex affettwata mill- età.
Temodal 2.5 mg/ ml powder for solution for infusion must be administered only by intravenous infusion.
Temodal 2. 5 mg/ ml trab għal soluzzjoni għall- infużjoni għandu jingħata biss permezz ta ’ infużjoni għal ġol- vina.
It must not be given by other routes of administration, such as the intrathecal, intramuscular, or subcutaneous route.
M’ għandux jingħata bl- ebda mod ieħor, bħal intratekali, intramuskolari jew taħt il - ġilda.
The appropriate dose of TMZ should be infused intravenously using a pump over a period of 90 minutes.
Id- doża xierqa ta ’ TMZ għandha tiġi infuża minn ġol- vina permezz ta ’ pompa fuq perijodu ta ’ 90 minuta.
94 As with other similar chemotherapeutic agents, caution is recommended to avoid extravasation.
94 Bħal sustanzi kimoterapewtiċi oħrajn, hija rakkomandata kawtela sabiex tkun evitata l- estravażjoni.
Local injection site adverse reactions, which were mostly mild and short-lived were reported in patients receiving Temodal 2.5 mg/ml powder for solution for infusion.
Reazzjonijiet avversi fis- sit mnejn tingħata l- injezzjoni, li kienu fil- parti l- kbira ħfief u ma damux, kienu rrappurtati f’ pazjenti li kienu qed jirċievu Temodal 2. 5 mg/ ml trab għal soluzzjoni għall - infużjoni.
Preclinical studies did not show permanent tissue damage (see sections 4.8 and 5.3).
Studji ta ’ qabel l- użu kliniku ma wrewx ħsara permanenti fit- tessuti (ara sezzjonijiet 4. 8 u 5. 3).
Temodal is also available as a hard capsule formulation (oral use).
Temodal jiġi wkoll fil- forma ta ’ kasula iebsa (użu orali).
Temodal 2.5 mg/ml powder for solution for infusion, given as an intravenous infusion over 90 minutes, is bioequivalent to the hard capsule formulation (see section 5.2).
Temodal 25 mg/ ml trab għal soluzzjoni għall- infużjoni, mogħti bħala infużjoni minn ġol- vina fuq 90 minuta, huwa bioekwivalenti għall- forma ta ’ kapsula iebsa (ara sezzjoni 5. 2).
Patients who received concomitant TMZ and RT in a pilot trial for the prolonged 42-day schedule were shown to be at particular risk for developing Pneumocystis carinii pneumonia (PCP).
Pazjenti li ngħataw TMZ flimkien ma ’ RT fi prova gwida għall- iskeda mtawla ta ’ 42 jum intwerew li kellhom riskju partikolari li taqbadhom pulmonite b ’ Pneumocystis carinii (PCP).
Thus, prophylaxis against PCP is required for all patients receiving concomitant TMZ and RT for the 42-day regimen (with a maximum of 49 days) regardless of lymphocyte count.
Għalhekk terapija biex tilqa ’ kontra PCP hija meħtieġa għal pazjenti kollha li qed jirċievu TMZ flimkien ma ’ RT għall - kors ta ’ 42 jum (b’ massimu ta ’ 49 jum) ikun x’ ikun l- għadd tal- limfoċiti.
There may be a higher occurrence of PCP when TMZ is administered during a longer dosing regimen.
Jista ’ jkun hemm aktar każijiet ta ’ PCP meta TMZ jingħata għal kors itwal.
Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukaemia, have also been reported very rarely (see section 4.8).
Każijiet ta ’ sindrome majelodisplastika u tumuri sekondarji, inkluża lewkimija majelojde, kienu wkoll irrappurtati b’ mod rari ħafna (ara sezzjoni 4. 8).
Nausea and vomiting are very commonly associated with TMZ.
Dardir u rimettar huma assoċjati b’ mod komuni ħafna ma ’ TMZ.
Adult patients with newly-diagnosed glioblastoma multiforme
Pazjenti b’ glioblastoma multiforme li tkun għada kif ġiet dijanjostikata
Anti-emetic prophylaxis is recommended prior to the initial dose of concomitant phase and it is strongly recommended during the monotherapy phase.
Kura biex tilqa ’ għat- tqallih hija rakkomandata qabel l- ewwel doża tal- fażi konkomitanti u hija rakkomandata ħafna waqt il- fażi ta ’ monoterapija.
Patients who have experienced severe (Grade 3 or 4) vomiting in previous treatment cycles may require anti-emetic therapy.
Pazjenti li fiċ- ċikli ta ’ kura li ngħataw qabel irrimettew ħafna (Grad 3 jew 4) jista ’ jkollhom bżonn terapija kontra t- tqallih.
Laboratory parameters
Parametri tal- laboratorju
Prior to dosing, the following laboratory parameters must be met:
Qabel id- dożaġġ, dawn il- parametri tal- laboratorji li ġejjin iridu jintlaħqu:
A complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until ANC > 1.5 x 109/l and platelet count > 100 x 109/l.
Għadd komplet tad- demm għandu jinkiseb fit- 22 Jum (21 jum wara l- ewwel doża) jew sa 48 siegħa minn dak il- jum, u kull ġimgħa sakemm l- ANC ikun > 1. 5 x 109/ l u l- għadd tal -
95 reduced one dose level (see section 4.2).
95 plejtlets ikun > 100 x 109/ l.
Elderly patients appear to be at increased risk of neutropenia and thrombocytopenia, compared with younger patients.
Pazjenti anzjani jidhru li huma f' riskju akbar li jkollhom newtropenja u tromboċitopenja, meta mqabbla ma ’ pazjenti iżgħar.
Men being treated with TMZ should be advised not to father a child up to 6 months after receiving the last dose and to seek advice on cryoconservation of sperm prior to treatment (see section 4.6).
Irġiel li qed ikunu ttrattati b’ TMZ huma kunsiljati biex ma jkollhomx tfal sa 6 xhur wara l- aħħar doża, u biex jieħdu parir dwar il- krijokonservazzjoni ta ’ l- isperma qabel il- kura (ara sezzjoni 4. 6).
This medicinal product contains 2.4 mmol sodium per vial.
Dan il- prodott mediċinali fih 2. 4 mmol sodium f’ kull kunjett.
This should be taken into consideration by patients on a controlled sodium diet.
Dan għandu jitqies minn pazjenti fuq dieta ristretta mis- sodium.
Interaction studies have only been performed in adults.
Studji ta ’ interazzjoni saru biss f’ adulti
In a separate phase I study, administration of TMZ with ranitidine did not result in alterations in the extent of absorption of temozolomide or the exposure to its active metabolite monomethyl triazenoimidazole carboxamide (MTIC).
Fi studju separat ta ’ Fażi I, l- għotja ta ’ TMZ ma ’ ranitidine ma bidilx il- grad ta ’ assorbiment ta ’ temozolomide jew l- esponiment għal- metabolu attiv tiegħu monomethyl triazenoimidazole carboxamide (MTIC).
Based on an analysis of population pharmacokinetics in phase II trials, co-administration of dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, H2 receptor antagonists, or phenobarbital did not alter the clearance of TMZ.
Ibbażat fuq analiżi tal- farmakokinetika tal- popolazzjoni minn provi ta ’ Fażi II, l- għoti flimkien ta ’ dexamethasone, prochlorperazine, phenytoin, carbamazepine, ondansetron, antagonisti tar- riċettur ta ’ l- H2, jew phenobarbital ma biddlux it- tneħħija ta ’ TMZ.
Co-administration with valproic acid was associated with a small but statistically significant decrease in clearance of TMZ.
L- għoti flimkien ma ’ valproic acid kien assoċjat ma ’ tnaqqis żgħir iżda statistikament sinifikanti fit- tneħħija ta ’ TMZ.
However, since TMZ does not undergo hepatic metabolism and exhibits low protein binding, it is unlikely that it would affect the pharmacokinetics of other medicinal products (see section 5.2).
Madankollu, billi TMZ ma jgħaddix minn metaboliżmu tal- fwied u ma tantx jeħel mal- proteini tad- demm, x’ aktarx li ma jaffettwax il- farmakokinetika ta ’ prodotti mediċinali oħra (ara sezzjoni 5. 2).
Temodal 2.5 mg/ml should not be administered to pregnant women.
Temodal 2. 5 mg/ ml m’ għandux jingħata lil nisa waqt it- tqala.
Lactation
Nisa li
96 It is not known whether TMZ is excreted in human milk; thus, breast-feeding should be discontinued while receiving treatment with TMZ.
96 potenzjalment jista ’ jkollhom it- tfal għandhom jingħataw il- parir biex jużaw metodu ta ’ kontraċezzjoni effettiv biex jevitaw li joħorġu tqal waqt li jkunu qed jirċievu TMZ.
Therefore, men being treated with it should be advised not to father a child up to 6 months after receiving the last dose and to seek advice on cryoconservation of sperm prior to treatment, because of the possibility of irreversible infertility due to therapy with TMZ.
Għalhekk, irġiel li qed ikunu ttrattati għandhom ikunu kkunsiljati biex ma jkollhomx tfal sa 6 xhur wara l- aħħar doża u biex jieħdu parir dwar il- krijokonservazzjoni ta ’ l- isperma qabel il- kura minħabba l- possibbiltà ta ’ infertilità irreversibbli minħabba t- terapija b’ TMZ.
Clinical trial experience with hard capsules
Esperjenza mill- provi kliniċi b’ kapsuli iebsin
In patients treated with TMZ, whether used in combination with RT or as monotherapy following RT for newly-diagnosed glioblastoma multiforme, or as monotherapy in patients with recurrent or progressive glioma, the reported very common adverse reactions were similar: nausea, vomiting, constipation, anorexia, headache and fatigue.
F’ pazjenti ikkurati b’ TMZ, kemm kombinat ma ’ RT jew bħala monoterapija wara RT għal glioblastoma multiforme li tkun għada kif ġiet dijanjostikata, jew bħala monoterapija waħdu f’ pazjenti b’ glijoma rikurrenti jew progressiva, l- effetti avversi komuni ħafna rappurtati kienu simili: tqallih, rimettar, stitikezza, anoressija, uġigħ ta ’ ras u għejja.
Convulsions were reported very commonly in the newly- diagnosed glioblastoma multiforme patients receiving monotherapy, and rash was reported very commonly in newly-diagnosed glioblastoma multiforme patients receiving TMZ concurrent with RT and also as monotherapy, and commonly in recurrent glioma.
Aċċessjonijiet kienu rappurtati komuni ħafna f’ pazjenti b’ glioblastoma multiforme li tkun għada kif ġiet dijanjostikata li kienu qed jirċievu monoterapija, u raxx kien rappurtat komuni ħafna f’ pazjenti b’ glioblastoma multiforme li tkun għada kif ġiet dijanjostikata li kienu qed jirċievu TMZ flimkien ma ’ RT kif ukoll bħala monoterapija u komuni b’ glijoma rikurrenti.
Most haematological adverse reactions were reported commonly or very commonly in both indications (Tables 4 and 5); the frequency of grade 3-4 laboratory findings is presented after each table.
Ħafna mir- reazzjonijet avversi ħematoloġiċi kienu rappurtati komuni jew komuni ħafna fiż- żewġ indikazzjonijiet (Tabelli 4 u 5); il- frekwenza ta ’ grad 3- 4 tas- sejbiet tal - laboratorju tidher wara kull tabella.
Blood and lymphatic system disorders Common:
97 Disturbi tad- demm u tas- sistema limfatika Komuni:
97 Endocrine disorders Uncommon:
Disturbi fis- sistema endokrinarja Mhux komuni:
Cushingoid
Cushingoid u n- nutrizzjoni
Metabolism and nutrition disorders Very common:
Komuni ħafna:
Cardiac disorders Uncommon:
Disturbi fil- qalb Mhux komuni
98 Respiratory, thoracic and mediastinal disorders Common:
Disturbi respiratorji, toraċiċi u medjastinali Komuni:
Common:
99 Komuni:
99 Common:
Komuni:
*A patient who was randomised to the RT arm only, received TMZ + RT.
għal fergħa ta ’ RT biss, ingħata TMZ + RT.
When laboratory abnormalities and adverse events were combined across concomitant and monotherapy treatment phases, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic events were observed in 8% of the patients.
Meta anormalitajiet tal- laboratorju u effetti avversi kienu kumbinati bejn il- fażijiet b’ kura meta ingħataw flimkien u b’ dik meta ngħata waħdu, anormalitajiet tan- newtrofili ta ’ Grad 3 jew Grad 4 inklużi effetti newtropeniċi dehru f’ 8% tal- pazjenti.
Grade 3 or Grade 4 thrombocyte abnormalities, including thrombocytopenic events were observed in 14% of the patients who received TMZ.
Anormalitajiet fit- tromboċiti ta ’ Grad 3 jew Grad 4 inklużi effetti tromboċitopeniċi deheru f’ 14% tal - pazjenti li ngħataw TMZ.
These reactions were usually Grade 1 or 2 (0 – 5 episodes of vomiting in 24 hours) and were either self-limiting or readily controlled with standard anti-emetic therapy.
Dawn ir- reazzjonijet kienu normalment Grad 1 jew 2 (0 – 5 episodji ta ’ rimettar f’ 24 siegħa) u jew waqfu waħidhom jew kienu kontrollati malajr b’ terapija kontra t- tqallih standard.
Table 5 includes adverse reactions reported during clinical trials for recurrent or progressive malignant glioma and following the marketing of Temodal.
Tabella 5 tinkludi reazzjonijiet avversi li kienu rrappurtati fi provi kliniċi għall- glijoma malinna rikurrenti jew progressiva u wara t- tqegħid fis- suq ta ’ Temodal.
Adverse reactions in patients with recurrent or progressive malignant glioma Infections and infestations
Reazzjonijiet avversi f’ pazjenti bi glijoma malinna rikurrenti jew progressiva
Headache Somnolence, dizziness, paresthesia
Ngħas, sturdament, parasteżija
Common:
100 Disturbi respiratorji, toraċiċi u medjastinali
Fatigue Fever, asthenia, rigors, malaise, pain, taste perversion
Għejja Deni, astenja, tertir, tħossok ma tiflaħx, uġigħ, perverżjoni tat- togħma
Allergic reactions, including anaphylaxis, angioedema
Reazzjonijiet allerġiċi, inkluża anafilassi, anġjoedima
In a population pharmacokinetics analysis of clinical trial experience there were 101 female and 169 male subjects for whom nadir neutrophil counts were available and 110 female and 174 male subjects for whom nadir platelet counts were available.
F’ analiżi bil- farmakokinetika ta’ popolazzjoni fl- esperjenza bi prova klinika kien hemm 101 mara u 169 raġel li għalihom il- valuri l- aktar baxxi tan- newtrofili kienu disponibbli u 110 mara u 174 raġel li għalihom il- valuri l- aktar baxxi tal- plejtlets kienu disponibbli.
There were higher rates of Grade 4 neutropenia (ANC < 0.5 x 109/l), 12% vs 5%, and thrombocytopenia (< 20 x 109/l), 9% vs 3%, in women vs men in the first cycle of therapy.
Kien hemm rati ogħla ta ’ newtropenja ta ’ Grad 4 (ANC < 0. 5 x109/ l), 12% vs 5%, u tromboċitopenja (< 20 x109/ l), 9% vs 3% fin- nisa vs l - irġiel fl- ewwel ċiklu tat- terapija.
In a 400 subject recurrent glioma data set, Grade 4 neutropenia occurred in 8% of female vs 4% of male subjects and Grade 4 thrombocytopenia in 8% of female vs 3% of male subjects in the first cycle of therapy.
F’ set ta ’ dejta rikurrenti għal glijoma b’ 400 individwu, newtropenja ta ’ Grad 4 seħħet fi 8% tan- nisa vs 4% ta ’ l- irġiel u tromboċitopenja ta ’ Grad 4 fi 8% tan- nisa vs 3% ta ’ l- irġiel fl- ewwel ċiklu tat- terapija.
In a study of 288 subjects with newly– diagnosed glioblastoma multiforme, Grade 4 neutropenia occurred in 3% of female vs 0% of male subjects and Grade 4 thrombocytopenia in 1% of female vs 0% of male subjects in the first cycle of therapy.
Fi studju b’ 288 individwu b’ glioblastoma multiforme li għada kif ġiet dijanjostikata, newtropinja ta ’ Grad 4 seħħet f’ 3% tan- nisa vs 0% ta ’ l- irġiel u tromboċitopenja ta ’ Grad 4 seħħet f’ 1% tan- nisa vs 0% ta ’ l- irġiel fl- ewwel ċiklu tat- terapija.
Clinical trial experience with IV
Esperjenza tal- prova klinika bl- IV
Temodal 2.5 mg/ml powder for solution for infusion delivers equivalent TMZ dose and exposure to both TMZ and its active metabolite MTIC as the corresponding Temodal hard capsules (see section 5.2).
Temodal 2. 5 mg/ ml trab għal soluzzjoni għall- infużjoni jipprovdi doża ta ’ TMZ ekwivalenti għall - esponiment kemm ta ’ TMZ kif ukoll tal- metabolu attiv tiegħu MTIC, bħal dik ta ’ Temodal kapsuli iebsin (ara sezzjoni 5. 2).
Adverse reactions reported during the two studies with the intravenous formulation (n=35) but not in studies using hard capsules, were infusion site reactions: pain, irritation, pruritus, warmth, swelling, and erythema, as well as haematoma.
Reazzjonijiet avversi rrappurtati waqt iż- żewġ studji bil- mod li jingħata minn ġol- vini (n=35) iżda li ma seħħewx bil- kapsuli iebsin, kienu reazzjonijiet tas- sit mnejn tingħata l - injezzjoni: uġigħ, irritazzjoni, ħakk, ħruq, nefħa u ħmura kif ukoll ematoma.
Post -Marketing Experience
Esperjenza ta ’ Wara t- Tqegħid fis- Suq
Cases of toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported very rarely.
101 Każijiet ta ’ nekrożi tossika tal- ġilda u sindrome ta ’ Stevens- Johnson kienu rrappurtati rari ħafna.
Doses of 500, 750, 1,000, and 1,250 mg/m2 (total dose per cycle over 5 days) have been evaluated clinically in patients.
Dożi ta ’ 500, 750, 1, 000, u 1, 250 mg/ m2 (doża totali kull ċiklu matul 5 ijiem) ġew evalwati klinikament f 'pazjenti.
An overdose of 10,000 mg (total dose in a single cycle, over 5 days) was taken by one patient and the adverse reactions reported were pancytopenia, pyrexia, multi-organ failure and death.
Doża eċċessiva ta ’ 10, 000 mg (doża totali f’ ċiklu wieħed, matul 5 ijiem) ittieħdet minn pazjent u l- effetti avversi rrappurtati kienu panċitopenja, deni, kollass ta ’ diversi organi u mewt.
There are reports of patients who have taken the recommended dose for more than 5 days of treatment (up to 64 days) with adverse events reported including bone marrow suppression, with or without infection, in some cases severe and prolonged and resulting in death.
Hemm rapporti ta ’ pazjenti li ħadu d- doża rrakkomandata għal aktar mill- 5 tijiem tat- trattament (sa 64 jum) b’ effetti avversi rrappurtati li jinkludu soppressjoni tal- mudullun, b’ infezzjoni jew mingħajr infezzjoni, f’ xi każijiet li kienu serji u fit- tul u li wasslu għall- mewt.
In the event of an overdose, haematological evaluation is needed.
Fil- każ ta ’ doża eċċessiva, evalwazzjoni ħematoloġika hija meħtieġa.
101 5.1 Pharmacodynamic properties
5. 1 Tagħrif farmakodinamiku
L01A X03
Aġenti antineoplastiċi – sustanzi alkylating oħra, kodiċi ATC L01A X03
The cytotoxicity of MTIC is thought to be due primarily to alkylation at the O6 position of guanine with additional alkylation also occurring at the N7 position.
Huwa maħsub li ċ- ċitotossiċità ta ’ MTIC hija primarjament minħabba l- alkylation f’ pożizzjoni O6 ta ’ guanine, b’ alkylation addizzjonali li sseħħ ukoll fil - pożizzjoni N7.
A total of 573 patients were randomised to receive either TMZ + RT (n=287) or RT alone (n=286).
Totall ta ’ 573 pazjent ġew randomised biex jirċievu TMZ + RT (n=287) jew RT waħdu (n=286).
Patients in the TMZ + RT arm received concomitant TMZ (75 mg/m2) once daily, starting the first day of RT until the last day of RT, for 42 days (with a maximum of 49 days).
Il - pazjenti fil- fergħa ta ’ TMZ + RT irċevew flimkien TMZ (75 mg/ m2) darba kuljum, bdew fl- ewwel jum ta ’ RT sa l- aħħar jum ta ’ RT għal 42 jum (sa mhux aktar minn 49 jum).
TMZ was administered as salvage therapy in the follow-up phase in 161 patients of the 282 (57%) in the RT alone arm, and 62 patients of the 277 (22%) in the TMZ + RT arm.
TMZ kien mogħti bħala terapija ta ’ salvataġġ fil- fażi ta ’ follow- up f’ 161 pazjent mill- 282 (57%) fil - fergħa b’ RT waħdu, u f’ 62 pazjent mill- 277 (22%) fil- fergħa ta ’ TMZ + RT.
The addition of concomitant TMZ to RT, followed by TMZ monotherapy in the treatment of patients with newly-diagnosed glioblastoma multiforme demonstrated a statistically significant improvement in overall survival (OS) compared with RT alone (Figure 1).
Iż- żieda ta ’ TMZ flimkien ma ’ RT, segwit b’ TMZ waħdu fil- kura ta’ pazjenti f’ glioblastoma multiforme li tkun għada kif ġiet dijanjostikata wasslet għal sopravivenza ġenerali (OS) aħjar b’ mod statistikament sinifikanti meta mqabbel ma ’ RT waħidha (Figura 1).
Kaplan-Meier curves for overall survival (Intent to Treat population)
Kurvi Kaplan- Meier għas- sopravivenza ġenerali (popolazzjoni Intent to Treat)
The results from the trial were not consistent in the subgroup of patients with a poor performance status (WHO PS=2, n=70), where overall survival and time to progression were similar in both arms.
Ir- riżultati mill- prova ma kienux konsistenti fis- sottogrupp ta ’ pazjenti bi statut ta ’ prestazzjoni dgħajjef (WHO PS=2, n=70), fejn is- sopravivenza ġenerali u ż- żmien biex javvanzaw kienu simili fiż - żewġ fergħat.