qanastek/EMEA-V3 huggingface dataset:
µg/week) (3 MIU TIW)
MIU TIW)
week) +
ġimgħa) +
p
Valur
value a
1, 200 mg) d
21% (9/43)
1, 200 mg) d
Genotype 1, 4
Kollox Ġenotip 1, 4
0.006
0. 047 0. 006
0.007
0. 017 0. 007
Overall Response1 (n=118)
Rispons Globali1 (n=118)
 39 Genotype 1 (n=92)
Ġenotip 1 (n=92)
 40 Table 6.
Tabella 6.
24 mg of powder (corresponding to 3 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml of water for injections in an ampoule (type I glass) with 1 injection syringe, 2 injection needles and 1 cleansing swab.
24 mg ta ’ trab (li jikkorrispondi għal 3 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) b’ siringa 1 għall- injezzjoni, 2 labar ta ’ l- injezzjoni u tajjara għat- tindif.
Pack sizes of 1
Pakketti ta ’ daqsijiet b’ 1
Or
u
24 mg of powder (corresponding to 3 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml of water for injections in an ampoule (type I glass) Pack sizes of 6 Not all pack sizes may be marketed.
24 mg ta ’ trab (li jikkorrispondi għal 3 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) Pakketti ta ’ daqsijiet b’ 6 Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
IntronA is supplied as a powder at strengths of 3 million IU/ml for single-dose use.
IntronA hu pprovdut bħala trab b’ qawwa ta ’ 3 miljun IU/ ml għall- użu f’ doża waħda.
 42 As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and discolouration prior to administration.
Bħal f’ kull prodott mediċinali li jingħata b’ injezzjoni, is- soluzzjoni rikostitwita għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
Preparation of IntronA for intravenous infusion:
Preparazzjoni ta ’ IntronA għall- infużjoni fil- vini:
 43 1.
1.
IntronA 5 million IU/ml powder and solvent for solution for injection or infusion
IntronA 5 miljun IU/ ml trab u solvent għal soluzzjoni għall- injezzjoni jew infużjoni
One vial of powder contains 5 million IU of interferon alfa-2b produced in E.coli by recombinant DNA technology.
Kull kunjett ta ’ trab fih 5 miljun IU ta ’ interferon alfa- 2b mgħamul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti.
After reconstitution, 1 ml contains 5 million IU of interferon alfa-2b.
Meta jkun rikostitwit, 1 ml jkun fih 5 miljun IU ta ’ interferon alfa- 2b.
 44 Combination therapy:
Terapija kombinata:
 45 (See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
(Ara l- SPC tal- kapsuli ribavirin u l- linji gwida għal tibdil fid- dożaġġ għal terapija kombinata.
 46 Chronic Myelogenous Leukaemia:
Lewkimja tal- Mudullun Kronika:
Interferon alfa -2b treatment is to be restarted at 50% of the previous dose.
It- trattament b’ interferon alfa- 2b għandu jerġa ’ jinbeda b’ 50% tad- doża ta ’ qabel.
If intolerance persists after dose adjustment or if granulocytes decrease to < 250/mm3 or ALT/AST rises to > 10 x upper limit of normal, discontinue interferon alfa -2b therapy.
Jekk l- intolleranza tippersisti wara l- aġġustament fid- doża jew jekk il - granuloċiti jonqsu għal < 250/ mm³ jew l- ALT/ AST jogħlew għal > 10 darbiet l- ogħla limitu tan - normal, waqqaf it- terapija b’ interferon alfa- 2b.
 47 Children and adolescents:
Tfal u adolexxenti:
 48 Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Infiltrazzjonijiet pulmonarji, pulmonite, u pnewmonja, li kultant wasslu għall- mewt, kienu innutati f’ każijiet rari fil- pazjenti ttrattati bl- interferon alpha, inklużi dawk ittrattati b’ IntronA.
 49 Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived albumin.
Tilqim xieraq (Epatite A u B) għandu jkun konsidrat għal pazjenti li jirċievu b’ mod regolari/ ripetut albumina li tkun ġejja mill- plażma tal- bniedem.
 50 ribavirin should be assessed in young children prior to the initiation of therapy.
Għalhekk ir- riskju/ benefiċċju ta ’ l - użu kombinat ta ’ interferon alfa- 2b u ribavirin għandu jiġi evalwat fi tfal żgħar qabel tinbeda t - terapija.
Mononeuropathies, coma
Newropatija periferali Emorraġija ċerebrovaskulari, iskemija ċerebrovaskulari, aċċessjoni, koxjenza indebolita, enċefalopatija Mononewropatiji, koma§
These undesirable effects have also been reported with Intron A alone.
Dawn l- effetti mhux mixtieqa kienu ukoll irrappurtati b’ IntronA waħdu.
Table 2 Adverse reactions very commonly and commonly reported in paediatric clinical trials Very common (≥1/10) - Common (≥1/100, < 1/10) System Organ Class
Reazzjonijiet avversi irrapurtati b’ mod komuni ħafna u komuni fil- provi kliniċi pedjatriċi Komuni ħafna (≥1/ 10) - Komuni (≥1/ 100, < 1/ 10)
Adverse Reactions
Klassi tas- sistema ta ’ l - organi Infezzjonijiet u infestazzjonijiet
 Infection and infestations
Reazzjonijiet avversi
 57 The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ir- riżultati ta ’ diversi studji jissuġġerixxu li, hekk kif ikun mqabbad mal- membrana taċ- ċellula, l - interferon jagħti bidu għal sekwenza kumplessa ta ’ okkorrenzi intraċellulari li jinkludu l- induzzjoni ta ’ ċerti enżimi.
 58 sustained response 6 months after 1 year of treatment than those who took < 80% of their treatment (56% vs.
Irrispettiv mill - ġenotip, il- pazjenti li rċivew IntronA flimkien ma ’ ribavirin u rċivew ≥ 80% tat- trattament tagħhom kellhom rispons sostnut ogħla 6 xhur wara sena ta ’ trattament minn dawk li ħadu < 80% tat- trattament tagħhom (56% vs.
 60 Genotype 1 (n=92)
Ġenotip 1 (n=92)
 61 Table 6.
Tabella 6.
24 mg of powder (corresponding to 5 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml water for injections in an ampoule (type I glass) with 1 injection syringe, 2 injection needles and 1 cleansing swab.
24 mg ta ’ trab (li jikkorrispondi għal 5 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) b’ siringa 1 għall- injezzjoni, 2 labar ta ’ l- injezzjoni u tajjara għat- tindif.
24 mg of powder (corresponding to 5 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml water for injections in an ampoule (type I glass) Pack sizes of 6 Not all pack sizes may be marketed.
24 mg ta ’ trab (li jikkorrispondi għal 5 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) Pakketti ta ’ daqsijiet b’ 6 Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
IntronA is supplied as a powder at strengths of 5 million IU/ml for single-dose use.
IntronA hu pprovdut bħala trab b’ qawwa ta ’ 5 miljun IU/ ml għall- użu f’ doża waħda.
 63 As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and discolouration prior to administration.
Bħal f’ kull prodott mediċinali li jingħata b’ injezzjoni, is- soluzzjoni rikostitwita għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
 64 1.
1.
IntronA 10 million IU/ml powder and solvent for solution for injection or infusion
IntronA 10 miljun IU/ ml trab u solvent għal soluzzjoni għall- injezzjoni jew infużjoni
One vial of powder contains 10 million IU of interferon alfa-2b produced in E.coli by recombinant DNA technology.
Kull kunjett ta ’ trab fih 10 miljun IU ta ’ interferon alfa- 2b mgħamul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti.
After reconstitution, 1 ml contains 10 million IU of interferon alfa-2b.
Meta jkun rikostitwit, 1 ml jkun fih 10 miljun IU ta ’ interferon alfa- 2b.
 65 Combination therapy:
Terapija kombinata:
 66 (See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
(Ara l- SPC tal- kapsuli ribavirin u l- linji gwida għal tibdil fid- dożaġġ għal terapija kombinata.
 67 Chronic Myelogenous Leukaemia:
Lewkimja tal- Mudullun Kronika:
As induction therapy, interferon alfa -2b is administered intravenously at a dose of 20 million IU/m2 daily for five days a week for a four-week period; the calculated interferon alfa-2b dose is added to sodium chloride 9 mg/ml (0.9%) solution for injection and administered as a 20- minute infusion (see section 6.6).
Bħala terapija ta ’ l- induzzjoni, l- interferon alfa- 2b jingħata ġol- vina b’ doża ta ’ 20 miljun IU/ m² kuljum għal ħamest ijiem fil- ġimgħa għal perijodu ta ’ erba ’ ġimgħat; id- doża kkalkulata ta ’ interferon alfa- 2b tiżdied ma ’ sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni u tingħata bħala infużjoni ta ’ 20 minuta (ara sezzjoni 6. 6).
 68 Children and adolescents:
Tfal u adolexxenti:
 69 Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Infiltrazzjonijiet pulmonarji, pulmonite, u pnewmonja, li kultant wasslu għall- mewt, kienu innutati f’ każijiet rari fil- pazjenti ttrattati bl- interferon alpha, inklużi dawk ittrattati b’ IntronA.
 70 Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived albumin.
Tilqim xieraq (Epatite A u B) għandu jkun konsidrat għal pazjenti li jirċievu b’ mod regolari/ ripetut albumina li tkun ġejja mill- plażma tal- bniedem.
Infrequently, adult patients treated for chronic hepatitis C with IntronA developed thyroid abnormalities, ei ther hypothyroidism or hyperthyroidism.
F’ każijiet mhux tas- soltu, pazjenti ttrattati b’ IntronA għall- epatite Ċ kronika żviluppaw anormalitajiet fit- tirojde, ipotirojdiżmu jew ipertirojdiżmu.
Prior to initiation of Intron A therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be treated with conventional therapy.
Qabel tinbeda t - terapija b’ IntronA, il- livelli ta ’ TSH għandhom jiġu evalwati u kwalunkwe anormalità fit- tirojde għandha tiġi kkurata b’ terapija konvenzjonali.
 71 ribavirin should be assessed in young children prior to the initiation of therapy.
Għalhekk ir- riskju/ benefiċċju ta ’ l - użu kombinat ta ’ interferon alfa- 2b u ribavirin għandu jiġi evalwat fi tfal żgħar qabel tinbeda t - terapija.
 78 The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ir- riżultati ta ’ diversi studji jissuġġerixxu li, hekk kif ikun mqabbad mal- membrana taċ- ċellula, l - interferon jagħti bidu għal sekwenza kumplessa ta ’ okkorrenzi intraċellulari li jinkludu l- induzzjoni ta ’ ċerti enżimi.
 79 sustained response 6 months after 1 year of treatment than those who took < 80% of their treatment (56% vs.
Irrispettiv mill - ġenotip, il- pazjenti li rċivew IntronA flimkien ma ’ ribavirin u rċivew ≥ 80% tat- trattament tagħhom kellhom rispons sostnut ogħla 6 xhur wara sena ta ’ trattament minn dawk li ħadu < 80% tat- trattament tagħhom (56% vs.
 81 Genotype 1 (n=92)
Ġenotip 1 (n=92)
 82 Table 6.
Tabella 6.
24 mg of powder (corresponding to 10 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml water for injections in an ampoule (type I glass) with 1 injection syringe, 2 injection needles and 1 cleansing swab.
24 mg ta ’ trab (li jikkorrispondi għal 10 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) b’ siringa 1 għall- injezzjoni, 2 labar ta ’ l- injezzjoni u tajjara għat- tindif.
Pack sizes of 1 and 10
Pakketti ta ’ daqsijiet b’ 1 jew 10
Pack sizes of 6 Not all pack sizes may be marketed.
24 mg ta ’ trab (li jikkorrispondi għal 10 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) Pakketti ta ’ daqsijiet b’ 6 Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
IntronA is supplied as a powder at strengths of 10 million IU/ml for single-dose use.
IntronA hu pprovdut bħala trab b’ qawwa ta ’ 10 miljun IU/ ml għall- użu f’ doża waħda.
 84 As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and discolouration prior to administration.
Bħal f’ kull prodott mediċinali li jingħata b’ injezzjoni, is- soluzzjoni rikostitwita għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
 85 1.
1.
IntronA 18 million IU/ml powder and solvent for solution for injection or infusion
IntronA 18- il miljun IU/ ml trab u solvent għal soluzzjoni għall- injezzjoni jew infużjoni
One vial of powder contains 18 million IU of interferon alfa-2b produced in E.coli by recombinant DNA technology.
Kull kunjett ta ’ trab fih 18- il miljun IU ta ’ interferon alfa- 2b mgħamul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti.
After reconstitution, 1 ml contains 18 million IU of interferon alfa-2b.
Meta jkun rikostitwit, 1 ml jkun fih 18- il miljun IU ta ’ interferon alfa- 2b.
The best way to use Intron A in this indication is in combination with ribavirin.
L- aħjar mod kif tuża IntronA f’ din l- indikazzjoni huwa flimkien ma ’ ribavirin.
 86 Combination therapy:
Terapija kombinata:
 87 (See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
(Ara l- SPC tal- kapsuli ribavirin u l- linji gwida għal tibdil fid- dożaġġ għal terapija kombinata.
 88 Chronic Myelogenous Leukaemia:
Lewkimja tal- Mudullun Kronika:
Therapy may continue for as long as the patient responds to interferon alfa -2b treatment.
It- terapija tista ’ titkompla sakemm il- pazjent jibqa ’ jirrispondi għat- trattament b’ interferon alfa- 2b.
If severe adverse events develop during interferon alfa -2b treatment, particularly if granulocytes decrease to < 500/mm3 or alanine aminotransferase/aspartate aminotransferase (ALT/AST) rises to > 5 x upper limit of normal, discontinue treatment temporarily until the adverse event abates.
Jekk iseħħu każijiet avversi severi matul it- trattament b’ interferon alfa- 2b, speċjalment jekk il - granuloċiti jonqsu għal < 500/ mm³ jew l- alanine aminotransferase/ aspartate aminotransferase (ALT/ AST) jogħlew għal > 5 darbiet l- ogħla limitu tan- normal, waqqaf it- trattament b' mod temporanju sakemm il- każ avvers ibatti.
 89 Children and adolescents:
Tfal u adolexxenti:
 90 Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Infiltrazzjonijiet pulmonarji, pulmonite, u pnewmonja, li kultant wasslu għall- mewt, kienu innutati f’ każijiet rari fil- pazjenti ttrattati bl- interferon alpha, inklużi dawk ittrattati b’ IntronA.
 91 Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived albumin.
Tilqim xieraq (Epatite A u B) għandu jkun konsidrat għal pazjenti li jirċievu b’ mod regolari/ ripetut albumina li tkun ġejja mill- plażma tal- bniedem.
 92 ribavirin should be assessed in young children prior to the initiation of therapy.
Għalhekk ir- riskju/ benefiċċju ta ’ l - użu kombinat ta ’ interferon alfa- 2b u ribavirin għandu jiġi evalwat fi tfal żgħar qabel tinbeda t - terapija.
 99 The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ir- riżultati ta ’ diversi studji jissuġġerixxu li, hekk kif ikun mqabbad mal- membrana taċ- ċellula, l - interferon jagħti bidu għal sekwenza kumplessa ta ’ okkorrenzi intraċellulari li jinkludu l- induzzjoni ta ’ ċerti enżimi.
 100 sustained response 6 months after 1 year of treatment than those who took < 80% of their treatment (56% vs.
Irrispettiv mill - ġenotip, il- pazjenti li rċivew IntronA flimkien ma ’ ribavirin u rċivew ≥ 80% tat- trattament tagħhom kellhom rispons sostnut ogħla 6 xhur wara sena ta ’ trattament minn dawk li ħadu < 80% tat- trattament tagħhom (56% vs.
pegylated
alfa- 2b pegilat
alfa-2b (100
(1. 5 µg/ kg / ġimgħa) +
(1.5 µg/kg/
µg/ ġimgħa) + ribavirin
value a
valur pb
valueb
1, 200 mg) d
 102 Genotype 1 (n=92)
Ġenotip 1 (n=92)
 103 Table 6.
Tabella 6.
24 mg of powder (corresponding to 18 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml water for injections in an ampoule (type I glass) with 1 injection syringe, 2 injection needles and 1 cleansing swab.
24 mg ta ’ trab (li jikkorrispondi għal 18- il MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) b’ siringa 1 għall- injezzjoni, 2 labar ta ’ l- injezzjoni u tajjara għat- tindif.
Pack sizes of 1 Not all pack sizes may be marketed.
Pakketti ta ’ daqsijiet b’ 1 Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
IntronA is supplied as a powder at strengths of 18 million IU/ml for single-dose use.
IntronA hu pprovdut bħala trab b’ qawwa ta ’ 18- il miljun IU/ ml għall- użu f’ doża waħda.
Vials must be reconstituted with 1 ml of water for injections.
Il- kunjetti jridu jkunu rrikostitwiti b’ 1 ml ta ’ ilma għall- injezzjonijiet.
 105 Preparation of IntronA for intravenous infusion:
Preparazzjoni ta ’ IntronA għall- infużjoni fil- vini:
 106 1.
1.
IntronA 30 million IU/ml powder and solvent for solution for injection or infusion
IntronA 30 miljun IU/ ml trab u solvent għal soluzzjoni għall- injezzjoni jew infużjoni
One vial of powder contains 30 million IU of interferon alfa-2b produced in E.coli by recombinant DNA technology.
Kull kunjett ta ’ trab fih 30 miljun IU ta ’ interferon alfa- 2b mgħamul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti.
After reconstitution, 1 ml contains 30 million IU of interferon alfa-2b.
Meta jkun rikostitwit, 1 ml jkun fih 30 miljun IU ta ’ interferon alfa- 2b.
 107 Combination therapy:
Terapija kombinata:
 108 (See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
(Ara l- SPC tal- kapsuli ribavirin u l- linji gwida għal tibdil fid- dożaġġ għal terapija kombinata.
 109 Chronic Myelogenous Leukaemia:
Lewkimja tal- Mudullun Kronika:
 110 Children and adolescents:
Tfal u adolexxenti:
 111 Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Infiltrazzjonijiet pulmonarji, pulmonite, u pnewmonja, li kultant wasslu għall- mewt, kienu innutati f’ każijiet rari fil- pazjenti ttrattati bl- interferon alpha, inklużi dawk ittrattati b’ IntronA.
 112 Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived albumin.
Tilqim xieraq (Epatite A u B) għandu jkun konsidrat għal pazjenti li jirċievu b’ mod regolari/ ripetut albumina li tkun ġejja mill- plażma tal- bniedem.
Determine TSH levels if, during the course of Intron A therapy, a patient develops symptoms consistent with possible thyroid dysfunction.
Stabilixxi l- livelli tat - TSH jekk, matul il- kors tat- terapija b’ IntronA, il- pazjent jiżviluppa sintomi konsistenti mal- possibbiltà ta ’ funzjoni ħażina tat- tirojde.
 113 ribavirin should be assessed in young children prior to the initiation of therapy.
Għalhekk ir- riskju/ benefiċċju ta ’ l - użu kombinat ta ’ interferon alfa- 2b u ribavirin għandu jiġi evalwat fi tfal żgħar qabel tinbeda t - terapija.
 120 The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ir- riżultati ta ’ diversi studji jissuġġerixxu li, hekk kif ikun mqabbad mal- membrana taċ- ċellula, l - interferon jagħti bidu għal sekwenza kumplessa ta ’ okkorrenzi intraċellulari li jinkludu l- induzzjoni ta ’ ċerti enżimi.
 121 sustained response 6 months after 1 year of treatment than those who took < 80% of their treatment (56% vs.
Irrispettiv mill - ġenotip, il- pazjenti li rċivew IntronA flimkien ma ’ ribavirin u rċivew ≥ 80% tat- trattament tagħhom kellhom rispons sostnut ogħla 6 xhur wara sena ta ’ trattament minn dawk li ħadu < 80% tat- trattament tagħhom (56% vs.
Patients were randomized to receive either pegylated interferon alfa-2b (1.5 µg/ kg/week) plus ribavirin (800 mg/day) or IntronA (3 MIU TIW) plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months.
Il- pazjenti kienu randomized biex jirċievu interferon alfa- 2b pegilat (1. 5 µg/ kg/ ġimgħa) flimkien ma ’ ribavirin (800 mg/ jum) jew inkella IntronA (3 MIU TIW) flimkien ma ’ ribavirin (800 mg/ jum) għal 48 ġimgħa b’ perijodu ta ’ follow- up ta ’ 6 xhur.
 123 Genotype 1 (n=92)
Ġenotip 1 (n=92)
Mean (% CV) multiple-dose pharmacokinetic parameters for IntronA and ribavirin capsules when administered to children or adolescents with chronic hepatitis C
Tabella 6 Medja (% CV) tal- parametri farmakokinetiċi b’ ħafna dożi għal IntronA u kapsuli ribavirin meta jingħataw lil tfal jew adolexxenti b’ epatite Ċ kronika IntronA
24 mg of powder (corresponding to 30 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml water for injections in an ampoule (type I glass) with 1 injection syringe, 2 injection needles and 1 cleansing swab.
24 mg ta ’ trab (li jikkorrispondi għal 30 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) b’ siringa 1 għall- injezzjoni, 2 labar ta ’ l- injezzjoni u tajjara għat- tindif.
IntronA is supplied as a powder at strengths of 30 million IU/ml for single-dose use.
IntronA hu pprovdut bħala trab b’ qawwa ta ’ 30 miljun IU/ ml għall- użu f’ doża waħda.
 126 Preparation of IntronA for intravenous infusion:
Preparazzjoni ta ’ IntronA għall- infużjoni fil- vini:
 127 1.
1.
IntronA 3 million IU/0.5 ml solution for injection or infusion
IntronA 3 miljun IU/ 0. 5 ml soluzzjoni għall- injezzjoni jew infużjoni
One vial of IntronA solution for injection or infusion, single dose vial, contains 3 million IU of recombinant interferon alfa-2b produced in E.coli by recombinant DNA technology, in 0.5 ml of solution.
Kunjett wieħed ta ’ IntronA soluzzjoni għall- injezzjoni jew infużjoni, kunjett b’ doża waħda, fih 3 miljun IU ta ’ interferon alfa- 2b rikombinanti magħmul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti, ġo 0. 5 ml ta ’ soluzzjoni.
Solution for injection or infusion Solution is clear and colourless.
Soluzzjoni għall- injezzjoni jew infużjoni Is- soluzzjoni hi ċara u bla kulur.
The combination of interferon alfa-2b and cytarabine (Ara-C) administered during the first 12 months of treatment has been demonstrated to significantly increase the rate of  128 major cytogenetic responses and to significantly prolong the overall survival at three years when compared to interferon alfa-2b monotherapy.
L- għoti ta ’ interferon alfa- 2b ma ’ cytarabine (Ara- C) matul l- ewwel 12- il xahar ta ’ trattament kien ppruvat li jżid b’ mod sinifikanti r- rata ta ’ rispons ċitoġenetiku maġġuri u li jtawwal b’ mod sinifikanti s- sopravivenza ġenerali wara tlett snin meta mqabbel mal- monoterapija b’ interferon alfa- 2b.
(See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
(Ara l- SPC tal- kapsuli ribavirin u l- linji gwida għal tibdil fid- dożaġġ għal terapija kombinata.
For paediatric patients who weigh < 47 kg or cannot swallow capsules, see
Għal pazjenti pedjatriċi li jiżnu < 47 kg jew li ma jistgħux jibilaw kapsuli, ara l- SPC tas- soluzzjoni orali ribavirin).
 130 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg).
Intwera li xi pazjenti bbenefikaw minn 5 miljun IU/ m2 IntronA mogħtija kuljum taħt il- ġilda flimkien ma ’ 20 mg/ m2 cytarabine (Ara- C) mogħtija kuljum taħt il- ġilda għal 10 ijiem kull xahar (sa doża massima ta ’ 40 mg kuljum).
Adjunctively with chemotherapy, interferon alfa -2b may be administered subcutaneously, at a dose of 5 million IU three times a week (every other day) for a duration of 18 months.
Bħala żieda mal- kemoterapija, interferon alfa- 2b jista ’ jingħata taħt il- ġilda, f’ doża ta ’ 5 miljun IU tliet darbiet fil- ġimgħa (darba kull jumejn) għal tul ta ’ 18- il xahar.
Children and adolescents:
konvenzjonali
 131
Tfal u adolexxenti:
Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Infiltrazzjonijiet pulmonarji, pulmonite, u pnewmonja, li kultant wasslu għall- mewt, kienu innutati f’ każijiet rari fil- pazjenti ttrattati bl- interferon alpha, inklużi dawk ittrattati b’ IntronA.
The  132 aetiology has not been defined.
L- etjoloġija ma kinetx definita.
 133 Combination therapy with ribavirin:
Terapija flimkien ma ’ ribavirin:
Prior to initiation of Intron A therapy for the treatment of chronic hepatitis C, evaluate serum thyroid-stimulating hormone (TSH) levels.
Qabel tibda t- terapija b’ IntronA għat- trattament ta ’ l - epatite Ċ kronika, qies l- livelli ta ’ l- ormoni li jistimulaw it- tirojde (TSH) fis- serum.
Therefore, the risk/benefit of the combined use of interferon alfa-2b and ribavirin should be assessed in young children prior to the initiation of therapy.
Għalhekk ir- riskju/ benefiċċju ta ’ l - użu kombinat ta ’ interferon alfa- 2b u ribavirin għandu jiġi evalwat fi tfal żgħar qabel tinbeda t - terapija.
Because of
L- aktar każijiet avversi komuni li huma potenzjalment ta ’ theddida għall- ħajja jew fatali li kienu rrappurtati jinkludu mukożite, dijarrea, newtropenja, indeboliment tal- kliewi, u disturbi fl- elettroliti.
 134 the risk of increased toxicity, careful adjustments of doses are required for IntronA and for the concomitant chemotherapeutic agents (see section 4.5).
Minħabba r- riskju ta ’ tossiċità akbar, jinħtieġu aġġustamenti bir- reqqa tad- dożi ta ’ IntronA u ta ’ s- sustanzi kemoterapewtiċi mogħtija b' mod konkomitanti (ara sezzjoni 4. 5).
 135 Women of childbearing potential have to use effective contraception during treatment.
Nisa li jista ’ jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt il- kura.
 136 Very rarely:
Rari ħafna:
Aplastic anaemia Pure red cell aplasia, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura
Lewkopenja Tromboċitopenja, limfadenopatija, limfopenija Anemija aplastika Aplasja taċ- ċelluli ħomor puri, purpura tromboċitopenika idjopatika, purpura trombotika tromboċitopenika
Endocrine disorders
Disturbi fis- sistema endokrinarja Komuni:
Sarcoidosis, exacerbation of sarcoidosis Systemic lupus erythematosus, vasculitis, rheumatoid arthritis (new or aggravated), Vogt-Koyanagi-Harada syndrome, acute hypersensitivity reactions including urticaria, angioedema, bronchoconstriction, anaphylaxis§
Sarkojdożi, tiħrax s- sarkojdożi Lupus erythematosus sistemika, vaskulite, artrite rewmatika (tibda jew taggrava), sindrome Vogt- Koyanagi- Harada, reazzjonijiet ta ’ sensittività eċċessiva akuti li jinkludu urtikarja, anġjoedema, bronkokostrizzjoni, anafilassi§ Ipotajrojdiżmu§, ipertajrojdiżmu§
Nervous system disorders§
Mhux magħruf § Disturbi fis- sistema nervuża
Ear and labyrinth
Disturbi fil- widnejn u fis- sistema labirintika
Retinal haemorrhages§, retinopathies (including macular oedema), retinal artery or vein obstruction§, optic neuritis, papilloedema, loss of visual acuity or visual field, cotton- wool spots§
Vista mċajpra Konġuntivite, vista anormali, disturbi fil- glandola tad - dmugħ, uġigħ fl- għajnejn Emoraġġiji fir- retina§, retinopatiji (inkluża edema makulari), ostruzzjoni fl- arterja jew vina tar- retina§, nevrite ottika, papilledema, tnaqqis fl- akutezza viżiva jew kamp viżiv, tikek qieshom tajjar§
Hepatomegaly Hepatotoxicity, (including fatality)
Epatomegalija Epatotossiċità, (inkluż fatalità)
Very common:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - ġilda Komuni ħafna:
Cardiomyopathy,
Każijiet avversi kardjovaskulari (CVS), b' mod partikolari arritmija, dehru li kienu korrelati l- aktar mal- mard CVS li kien jeżisti minn qabel u mat- terapija b’ sustanzi kardjotossiċi li saret qabel (ara sezzjoni 4. 4).
 138 that may be reversible upon discontinuation of interferon alpha, has been reported rarely in patients without prior evidence of cardiac disease (see section 4.4).
Kardjomajopatija li tista ’ tkun riversibbli bit- twaqqif ta ’ interferon alpha, kienet irrappurtata f’ każijiet rari f’ pazjenti li ma kellhomx evidenza minn qabel ta ’ mard tal- qalb (ara sezzjoni 4. 4).
Table 2 Adverse reactions very commonly and commonly reported in paediatric clinical trials Very common (≥1/10) - Common (≥1/100, < 1/10) System Organ Class Infection and infestations
Reazzjonijiet avversi irrapurtati b’ mod komuni ħafna u komuni fil- provi kliniċi pedjatriċi Komuni ħafna (≥1/ 10) - Komuni (≥1/ 100, < 1/ 10)
Metabolism and nutrition
Disturbi fil- metaboliżmu u n- nutrizzjoni
Psychiatric disorders§
Komuni: § Disturbi psikjatriċi
 140 4.9 Overdose
4. 9 Doża eċċessiva
The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ir- riżultati ta ’ diversi studji jissuġġerixxu li, hekk kif ikun mqabbad mal- membrana taċ- ċellula, l - interferon jagħti bidu għal sekwenza kumplessa ta ’ okkorrenzi intraċellulari li jinkludu l- induzzjoni ta ’ ċerti enżimi.
 141 Current clinical experience in patients who remain on interferon alfa-2b for 4 to 6 months indicates that therapy can produce clearance of serum HBV-DNA.
L- esperjenza klinika attwali f’ pazjenti li jibqgħu fuq l- interferon alfa- 2b minn 4 sa 6 xhur tindika li t - terapija tista ’ tipproduċi l- eliminazzjoni ta ’ l- HBV- DNA mis- serum.
32% in trial C/I 98-580).
32% fil- prova C/ I98- 580).
 143 Table 4
Tabella 4
interferon
µg/ ġimgħa) +
or
(3
150c µg/week) (3 MIU TIW)
MIU TIW)
d
1, 200 mg) d
1, 200 mg)
Kollox Ġenotip 1, 4
d
27% (56/ 205) 17% (21/ 125)
All Genotype 1, 4
0. 047 0. 006
 144, the benefit/risk of the combination of ribavirin and interferon alfa-2b needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8).
Minħabba nuqqas ta ’ dejta fi tfal b’ avvanz sever tal - marda, u l- potenzjal ta ’ effetti sekondarji, il- benefiċċju/ riskju tat- taħlita ta ’ ribavirin ma ’ interferon alfa- 2b għandha titqies bl- attenzjoni f’ din il- popolazzjoni (ara sezzjonijiet 4. 1, 4. 4 u 4. 8).
Overall Response1
Rispons Globali1 (n=118)
 145 Table 6.
Tabella 6.
Disodium phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, Edetate disodium,
Disodium phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, Edetate disodium, Sodium chloride, M- cresol, Polysorbate 80, Ilma għall- injezzjonijiet.
Within its shelf-life, for the purpose of transport, the solution can be kept at or below 25ºC for a period up to seven days before use.
Fil- perijodu ta ’ meta jkun għadu tajjeb, għal skopijiet ta ’ trasport, is- soluzzjoni tista ’ tinżamm f’ temperatura ta ’ 25°C jew anqas għal perijodu ta ’ mhux aktar minn sebat ijiem qabel l- użu.
IntronA can be put back in the refrigerator at any time during this seven- day period.
IntronA jista ’ jitpoġġa lura fil- friġġ fi kwalunkwe ħin f’ dawn is- sebat ijiem.
If the product is not used during the seven-day period, it cannot be put back in the refrigerator for a new storage period and must be discarded.
Jekk il- prodott ma jintużax matul dawn is- sebat ijiem, dan għandu jintrema. Jekk il- prodott ma jkunx intuża matul il- perijodu ta ’ sebat ijiem, ma jistax jitpoġġa lura fil- friġġ għal perijodu ġdid ta ’ ħażna u għandu jintrema.
0.5 ml of solution (corresponding to 3 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in an flip-off seal (aluminium) with a bonnet (polypropylene).
soluzzjoni ta ’ 0. 5 ml (li jikkorrispondi għal 3 MIU) f’ kunjett (ħġieġ tat- tip I), b’ tapp (lasktu halobutyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene).
0.5 ml of solution (corresponding to 3 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in an flip-off seal (aluminium) with a bonnet (polypropylene). with 1 injection syringe, 1 injection needle and 1 cleansing swab.
soluzzjoni ta ’ 0. 5 ml (li jikkorrispondi għal 3 MIU) f’ kunjett (ħġieġ tat- tip I), b’ tapp (lasktu halobutyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene). b’ siringa 1 għall- injezzjoni, labra 1 ta ’ l- injezzjoni u tajjara għat- tindif.
Packs sizes of 1, 6 or 12.
Pakketti ta ’ daqsijiet b’ 1, 6 jew 12.
IntronA solution for injection or infusion, may be injected directly after withdrawal of the appropriate doses from the vial with a sterile injection syringe.
IntronA, soluzzjoni għall- injezzjoni jew infużjoni, jista ’ jkun injettat immedjatament wara li jinġibdu d- dożi xierqa mill- kunjett b’ siringa ta ’ l- injezzjoni sterili.
The infusion is to be prepared immediately prior to use.
L- infużjoni għandha tkun ippreparata immedjatament qabel l- użu.
Any size vial may be used to measure the required dose; however, final concentration of interferon in sodium chloride solution must be not less than 0.3 million IU/ml.
Jista ’ jintuża kull daqs ta ’ kunjett biex titkejjel id- doża l- meħtieġa; madankollu, il- konċentrazzjoni finali ta ’ l- interferon fis- soluzzjoni tas- sodium chloride ma ’ tistax tkun inqas minn 0. 3 miljun IU/ ml.
The appropriate dose of IntronA is withdrawn from the vial(s), added to 50 ml of 9 mg/ml (0.9%) sodium chloride solution for injection in a PVC bag or glass bottle for intravenous use and administered over 20 minutes.
Id- doża korretta ta ’ IntronA tinġibed mill- kunjett/ i, tiżdied ma ’ 50 ml ta ’ 9 mg/ ml (0. 9%) sodium chloride soluzzjoni għall- injezzjoni f’ borża tal- PVC jew fi flixkun tal- ħġieġ għall- użu fil- vini, u tingħata fuq medda ta ’ 20 minuta.
NO OTHER MEDICINAL PRODUCT CAN BE INFUSED CONCOMITANTLY WITH INTRONA.
L- EBDA PRODOTT MEDIĊINALI IEĦOR M’ GĦANDU JITĦALLAT MA ’ L- INFUŻJONI TA ’ INTRONA
 147 As with all parenteral medicinal products, prior to administration inspect IntronA, solution for injection or infusion, visually for particulate matter and discolouration.
Bħal f’ kull prodott mediċinali parenterali, IntronA, soluzzjoni għall- injezzjoni jew infużjoni, għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
The solution should be clear and colourless.
Is- soluzzjoni għandha tkun ċara u bla kulur.
 148 1.
1.
IntronA 5 million IU/0.5 ml solution for injection or infusion
IntronA 5 miljun IU/ 0. 5 ml soluzzjoni għall- injezzjoni jew infużjoni
One vial of IntronA solution for injection or infusion, single dose vial, contains 5 million IU of recombinant interferon alfa-2b produced in E.coli by recombinant DNA technology, in 0.5 ml of solution.
Kunjett wieħed ta ’ IntronA soluzzjoni għall- injezzjoni jew infużjoni, kunjett b’ doża waħda, fih 5 miljun IU ta ’ interferon alfa- 2b rikombinanti magħmul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti, ġo 0. 5 ml ta ’ soluzzjoni.
CLINIC AL PARTICULARS
TAGĦRIF KLINIKU
The combination of interferon alfa-2b and cytarabine (Ara-C) administered during the first 12 months of treatment has been demonstrated to significantly increase the rate of  149 major cytogenetic responses and to significantly prolong the overall survival at three years when compared to interferon alfa-2b monotherapy.
L- għoti ta ’ interferon alfa- 2b ma ’ cytarabine (Ara- C) matul l- ewwel 12- il xahar ta ’ trattament kien ppruvat li jżid b’ mod sinifikanti r- rata ta ’ rispons ċitoġenetiku maġġuri u li jtawwal b’ mod sinifikanti s- sopravivenza ġenerali wara tlett snin meta mqabbel mal- monoterapija b’ interferon alfa- 2b.
Treatment should be dis continued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe thrombocytopaenia (< 70,000/mm3).
It- trattament għandu jitwaqqaf f’ każijiet ta ’ lewkopenja severa (< 1, 200/ mm3), ta ’ newtropenja severa (< 750/ mm3) jew ta ’ tromboċitopenija severa (< 70, 000/ mm3).
 151 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg).
Intwera li xi pazjenti bbenefikaw minn 5 miljun IU/ m2 IntronA mogħtija kuljum taħt il- ġilda flimkien ma ’ 20 mg/ m2 cytarabine (Ara- C) mogħtija kuljum taħt il- ġilda għal 10 ijiem kull xahar (sa doża massima ta ’ 40 mg kuljum).
In patients who are in the plateau phase (more than 50% reduction of myeloma protein) following initial induction chemotherapy, interferon alfa -2b may be administered as monotherapy, subcutaneously, at a dose of 3 million IU/m2 three times a week (every other day).
Fil- pazjenti li jinsabu fil- fażi ta ’ stabbiltà (aktar minn 50% tnaqqis tal- proteina tal- majeloma) wara kemoterapija ta ’ l- induzzjoni inizjali, interferon alfa- 2b jista ’ jingħata bħala monoterapija, taħt il- ġilda, f’ doża ta ’ 3 miljun IU/ m2 tliet darbiet fil- ġimgħa (darba kull jumejn).
CHOP -like regimens are advised, but clinical experience is available only with CHVP (combination of cyclophosphamide, doxorubicin, teniposide and prednisolone).
Korsijiet li jixbħu lil dak taċ- CHOP huma rakkomandati, iżda teżisti biss esperjenza klinika bis- CHVP (kumbinazzjoni ta ’ cyclophosphamide, doxorubicin, teniposide u prednisolone).
 152
Tfal u adolexxenti:
The  153 aetiology has not been defined.
L- etjoloġija ma kinetx definita.
 154 Combination therapy with ribavirin:
Terapija flimkien ma ’ ribavirin:
The mechanism by which Intron A may alter thyroid status is unknown.
Il- mekkaniżmu kif IntronA jista ’ jbiddel l- istat tat- tirojde mhuwiex magħruf.
 155 the risk of increased toxicity, careful adjustments of doses are required for IntronA and for the concomitant chemotherapeutic agents (see section 4.5).
Minħabba r- riskju ta ’ tossiċità akbar, jinħtieġu aġġustamenti bir- reqqa tad- dożi ta ’ IntronA u ta ’ s- sustanzi kemoterapewtiċi mogħtija b' mod konkomitanti (ara sezzjoni 4. 5).
 156 Women of childbearing potential have to use effective contraception during treatment.
Nisa li jista ’ jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt il- kura.
 157 Table 1.
Tabella 1:
Not known: § Immune system disorders
Mhux magħruf: § Disturbi fis- sistema immuni
Very rarely: § Psychiatric disorders
Rari ħafna: § Disturbi psikjatriċi
 159 The undesirable effects seen with hepatitis C are representative of those reported when IntronA is administered in other indications, with some anticipated dose-related increases in incidence.
L- effetti mhux mixtieqa li dehru ma ’ l- epatite Ċ huma rappreżentattivi ta ’ dawk irrappurtati meta IntronA jingħata f’ indikazzjonijiet oħra, b’ xi żidiet mistennija fl- inċidenza konnessi mad- doża.
 160 Neoplasms benign, malignant and unspecified (including cysts and polyps) Common:
Komuni:
Common: § See section 4.4
Komuni: § Ara sezzjoni 4. 4 4. 9 Doża eċċessiva
Any or all of these activities may contribute to interferon's therapeutic effects.  162 Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and human cell culture systems as well as human tumour xenografts in animals.
L- interferon alfa- 2b rikombinanti wera effetti antiproliferattivi fi studji fejn intużaw kemm sistemi ta ’ kultura ta ’ ċelluli umani u ta ’ l- annimali kif ukoll xenografts ta ’ tumur uman fl- annimali.
 2 million copies/ml Genotype 1
Ġenotip 1  2 miljun kopja/ ml Ġenotip 1
 164 Table 4
Tabella 4
after IntronA in combination with combination with ribavirin in
alfa- 2b pegilat
Study 11
IntronA
Study 22 pegylated
(1. 5 µg/ kg /
interferon
(3
alfa-2b (100
MIU TIW)
alfa-2b
ġimgħa) + ribavirin
IntronA
(3 MIU TIW) +
(1.5 µg/kg/
ribavirin (800 -
1, 200 mg)
1, 200 mg) d
 165, the benefit/risk of the combination of ribavirin and interferon alfa-2b needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8).
Minħabba nuqqas ta ’ dejta fi tfal b’ avvanz sever tal - marda, u l- potenzjal ta ’ effetti sekondarji, il- benefiċċju/ riskju tat- taħlita ta ’ ribavirin ma ’ interferon alfa- 2b għandha titqies bl- attenzjoni f’ din il- popolazzjoni (ara sezzjonijiet 4. 1, 4. 4 u 4. 8).
Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up period
Defimit bħala HCV- RNA taħt il- limitu li jista ’ jitkejjel b’ assay RT- PCR bażat fuq riċerka fl- aħħar tal- kura u waqt il - perijodu ta ’ follow- up 5. 2 Tagħrif farmakokinetiku
 166 Table 6.
Tabella 6.
0.5 ml of solution (corresponding to 5 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene).
soluzzjoni ta ’ 0. 5 ml (li jikkorrispondi għal 5 MIU) f’ kunjett (ħġieġ tat- tip I), b’ tapp (lasktu halobutyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene).
Pack sizes of 1
Pakketti ta ’ daqsijiet b’ 1 u
0.5 ml of solution (corresponding to 5 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) with 1 injection syringe, 1 injection needle and 1 cleansing swab.
soluzzjoni ta ’ 0. 5 ml (li jikkorrispondi għal 5 MIU) f’ kunjett (ħġieġ tat- tip I), b’ tapp (lasktu halobutyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene). b’ siringa 1 għall- injezzjoni, labra 1 ta ’ l- injezzjoni u tajjara għat- tindif.
 168 As with all parenteral medicinal products, prior to administration inspect IntronA, solution for injection or infusion, visually for particulate matter and discolouration.
Bħal f’ kull prodott mediċinali parenterali, IntronA, soluzzjoni għall- injezzjoni jew infużjoni, għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
23 May 2005
9 ta ’ Marzu 2000 Data ta ’ l- aħħar tiġdid:
10.
23 Mejju 2005 10.
 169 1.
1.
IntronA 10 million IU/ml solution for injection or infusion
IntronA 10 miljun IU/ ml soluzzjoni għall- injezzjoni jew infużjoni
One vial of IntronA solution for injection or infusion, single dose vial, contains 10 million IU of recombinant interferon alfa-2b produced in E.coli by recombinant DNA technology, in 1 ml of solution.
Kunjett wieħed ta ’ IntronA soluzzjoni għall- injezzjoni jew infużjoni, kunjett b’ doża waħda, fih 10 miljun IU ta ’ interferon alfa- 2b rikombinanti magħmul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti, ġo 1 ml ta ’ soluzzjoni.
The combination of interferon alfa-2b and cytarabine (Ara-C) administered during the first 12 months of treatment has been demonstrated to significantly increase the rate of
L- għoti ta ’ interferon alfa- 2b ma ’ cytarabine (Ara- C) matul l- ewwel 12- il xahar ta ’ trattament kien ppruvat li jżid b’ mod sinifikanti r- rata ta ’ rispons ċitoġenetiku maġġuri u li jtawwal b’ mod sinifikanti s- sopravivenza ġenerali wara tlett snin meta mqabbel mal- monoterapija b’ interferon alfa- 2b.
 172 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg).
Intwera li xi pazjenti bbenefikaw minn 5 miljun IU/ m2 IntronA mogħtija kuljum taħt il- ġilda flimkien ma ’ 20 mg/ m2 cytarabine (Ara- C) mogħtija kuljum taħt il- ġilda għal 10 ijiem kull xahar (sa doża massima ta ’ 40 mg kuljum).
 173
Tfal u adolexxenti:
The  174 aetiology has not been defined.
L- etjoloġija ma kinetx definita.
 175 Combination therapy with ribavirin:
Terapija flimkien ma ’ ribavirin:
 176 the risk of increased toxicity, careful adjustments of doses are required for IntronA and for the concomitant chemotherapeutic agents (see section 4.5).
Minħabba r- riskju ta ’ tossiċità akbar, jinħtieġu aġġustamenti bir- reqqa tad- dożi ta ’ IntronA u ta ’ s- sustanzi kemoterapewtiċi mogħtija b' mod konkomitanti (ara sezzjoni 4. 5).
 177 Women of childbearing potential have to use effective contraception during treatment.
Nisa li jista ’ jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt il- kura.
 178 Table 1.
Tabella 1:
 180 The undesirable effects seen with hepatitis C are representative of those reported when IntronA is administered in other indications, with some anticipated dose-related increases in incidence.
L- effetti mhux mixtieqa li dehru ma ’ l- epatite Ċ huma rappreżentattivi ta ’ dawk irrappurtati meta IntronA jingħata f’ indikazzjonijiet oħra, b’ xi żidiet mistennija fl- inċidenza konnessi mad- doża.
 181 Neoplasms benign, malignant and unspecified (including cysts and polyps) Common:
Komuni:
Any or all of these activities may contribute to interferon's therapeutic effects.  183 Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and human cell culture systems as well as human tumour xenografts in animals.
L- interferon alfa- 2b rikombinanti wera effetti antiproliferattivi fi studji fejn intużaw kemm sistemi ta ’ kultura ta ’ ċelluli umani u ta ’ l- annimali kif ukoll xenografts ta ’ tumur uman fl- annimali.
 185 Table 4
Tabella 4
 186, the benefit/risk of the combination of ribavirin and interferon alfa-2b needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8).
Minħabba nuqqas ta ’ dejta fi tfal b’ avvanz sever tal - marda, u l- potenzjal ta ’ effetti sekondarji, il- benefiċċju/ riskju tat- taħlita ta ’ ribavirin ma ’ interferon alfa- 2b għandha titqies bl- attenzjoni f’ din il- popolazzjoni (ara sezzjonijiet 4. 1, 4. 4 u 4. 8).
 187 Table 6.
Tabella 6.
1 ml of solution (corresponding to 10 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene).
soluzzjoni ta ’ 1 ml (li jikkorrispondi għal 10 MIU) f’ kunjett (ħġieġ tat- tip I), b’ tapp (lasktu halobutyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene).
1 ml of solution (corresponding to 10 MIU) in a vial (type I glass), with a stopper (halobutyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) with 1 injection syringe, 1 injection needle and 1 cleansing swab.
soluzzjoni ta ’ 1 ml (li jikkorrispondi għal 10 MIU) f’ kunjett (ħġieġ tat- tip I), b’ tapp (lasktu halobutyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene). b’ siringa 1 għall- injezzjoni, labra 1 ta ’ l- injezzjoni u tajjara għat- tindif.
Packs sizes of 1, 6 or 12 Not all pack sizes may be marketed.
Pakketti ta ’ daqsijiet b’ 1, 6 jew 12.
 189 As with all parenteral medicinal products, prior to administration inspect IntronA, solution for injection or infusion, visually for particulate matter and discolouration.
Bħal f’ kull prodott mediċinali parenterali, IntronA, soluzzjoni għall- injezzjoni jew infużjoni, għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
 190 1.
1.
IntronA 18 million IU/3 ml solution for injection or infusion
IntronA 18- il miljun IU/ 3 ml soluzzjoni għall- injezzjoni jew infużjoni