qanastek/EMEA-V3 huggingface dataset:
49 Duration of treatment - Retreatment Predictability of sustained virological response:
Kemm għandha ddum il- kura – Trattament mill- ġdid Kemm jista ’ jiġi mbassar r- rispons viroloġiku sostnut:
Vial/Pen Strength
Amministra Qawwa tal -
Administer Vial/Pen Once Weekly Strength
Pinna/ Kunjett (μg/ 0. 5ml)
Administer Once Weekly
Darba fil - Pinna/ Kunjett Ġimgħa (μg/ 0. 5ml) (ml)
(μg/0.5 ml)
Darba fil - Ġimgħa (ml)
(ml)
50 80
50* 50* 50* 50 50 50 80
0. 5 0. 4
50 Combination Therapy Dose Reduction Guidelines
Linji Gwida Dwar it- Tnaqqis fid- Doża tat- Terapija Kombinata
< 25 x 109/l 2.5 x ULN** > 4 mg/dl (for > 4 weeks)
> 4 mg/ dl > 4 ġimgħat)
Once Weekly
Kunjett/ Pinna (μg/ 0. 5 ml)
(μ g/0.5 ml)
Darba fil - Ġimgħa (ml)
51 Dose reduction for patients who use 0.5 μg/kg PegIntron monotherapy must be accomplished by reducing the prescribed volume by one-half.
Tnaqqis fid- doża għal pazjenti li jużaw il- monoterapija ta ’ PegIntron 0. 5 μg/ kg għandu jinkiseb billi jitnaqqas il- volum preskritt bin- nofs.
(μ g/0.5ml)
Intenzjonat (μg)
53 Hydration:
Idratazzjoni:
Infrequently, patients treated for chronic hepatitis C with interferon alpha have developed thyroid abnormalities, ei ther hypothyroidism or hyperthyroidism.
Mhux ta ’ spiss, pazjenti b’ epatite Ċ li ngħataw interferon alfa żviluppaw bidliet fit - tirojde, b’ mod li jew bdiet taħdem aktar mgħaġġla jew inkella aktar bil- mod.
54 Haematological abnormalities in HCV/HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
Patients treated with Peg Intron and ribavirin combination therapy and zidovudine are at increased risk of developing anaemia and therefore the concomitant use of this combination with zidovudine is not recommended (see section 4.5).
Pazjenti kkurati b’ terapija bit- taħlita ta ’ PegIntron u ribavrin ma ’ zidovudine għandhom riskju akbar li jiżviluppaw anemija u għalhekk l- użu ta ’ din it- taħlita ma ’ zidovudine mhux rakkomandata (ara sezzjoni 4. 5).
Caution is therefore advised when Peg Intron treatment is initiated for chronic hepatitis in patients treated with medication with a narrow therapeutic window and sensitive to mild metabolic impairment of the liver.
Il- kawtela għalhekk hija konsiljata meta tinbeda l- kura b’ PegIntron f’ pazjenti b’ epatite C kronika kkurati b’ mediċini li għandhom firxa terapewtika dejqa u li jkunu sensittivi għal indeboliment ħafif tal- fwied.
56 childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Nisa li jista ’ jkollhom it- tfal u s- sieħba tagħhom għandhom jużaw kontraċezzjoni effettiva kull wieħed waqt il- kura u għal 4 xhur wara li tkun intemmet il- kura.
57 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Confusion, tremor, ataxia, neuralgia, vertigo, paresthesia, hypoaesthesia, hyperaesthesia, hypertonia, migraine, increased sweating
Konfużjoni, tregħid, atassja, newralġja, vertigo, parasteżija, iposteżija, iperesteżija, ipertonija, emigranja, żieda fl- għaraq Attakk tal- qamar, newropatija periferali Emorraġija ċerebrovaskulari, iskemija ċerebrovaskulari,
Interstitial lung disease 58
Disturbi gastro- intestinali Komuni ħafna:
Rhabdomyolysis, myositis Renal and urinary disorders Common:
Disturbi fil- kliewi u fis - sistema urinarja
Reproductive system and breast disorders
Indeboliment renali, insuffiċjenza renali Disturbi fis- sistema riproduttiva u fis- sider Komuni:
There were some cases of more severe neutropenia in patients treated with the recommended doses of Peg Intron in combin ation with ribavirin (WHO grade 3:
Kien hemm xi każijiet ta ’ newtropenja iktar qawwija f’ pazjenti li ġew trattati bid- dożi rakkomandati ta ’ PegIntron flimkien ma 'ribavirin (Gradi ta ’ WHO 3:
59 Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
Każijiet avversi kardjovaskulari (CVS), l- aktar arritmija, dehru li kellhom x’ jaqsmu l- aktar ma ’ mard pri - eżistenti CVS u ma ’ l- għotja ta ’ aġenti kardjotossiċi xi darba qabel (ara sezzjoni 4. 4).
60 treatment and close observation of the patient are recommended in cases of overdose.
M’ hemm l- ebda antidotu speċifiku għal PegIntron; għalhekk, kura sintomatika o osservaz+zjoni mill- qrib tal- pazjent hija rakkomandata f’ każijiet ta ’ doża eċċessiva.
Neutrophil and white cell count reductions at the end of week 4 correlated with the dose of Peg Intron.
Tnaqqis fl- għadd ta ’ newtrofili u ċelloli bojod fl- aħħar tar- raba ġimgħa kien korrelatat mad- doża ta ’ PegIntron.
Peg Intron clinical trials – Naïve patients Two pivotal trials have been conducted, one (C/I97-010) with PegIntron monotherapy; the other (C/I98-580) with PegIntron in combination with ribavirin.
Studji Kliniċi fuq PegIntron - Pazjenti li qatt ma kienu ħadu din il- kura qabel Saru żewġ studji pivitali, wieħed (C/ I97- 010) b’ monoterapija b’ Pegintron u l- ieħor (C/ I98- 580) b’ PegIntron flimkien ma 'ribavirin.
This study showed that PegIntron was superior to interferon alfa-2b (Table 5).
Dan l- istudju wera li PegIntron kien superjuri għal interferon alfa- 2b (Tabella 5).
61 In the PegIntron combination trial, 1,530 naïve patients were treated for one year with one of the following combination regimens: • PegIntron (1.5 micrograms/kg/week) + ribavirin (800 mg/day), (n = 511). • PegIntron (1.5 micrograms/kg/week for one month followed by 0.5 microgram/kg/week for 11 months) + ribavirin (1,000/1,200 mg/day), (n = 514). • Interferon alfa-2b (3 MIU three times a week) + ribavirin (1,000/1,200 mg/day) (n = 505).
Fi prova fejn PegIntron intuża f’ kombinazzjoni, 1, 530 pazjent naïve ingħataw trattament għal sena b’ wieħed mill- korsijiet ikkumbinati li ġejjin: • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) + ribavirin (800 mg kuljum), (n = 511). • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwit 0. 5 mikrogrammi/ kg/ ġimgħa għal ħdax - il xahar) + ribavirin (1, 000/ 1, 200 mg kuljum), (n = 514). • Interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg kuljum) (n = 505).
Treatment regimen
Kors ta ’ trattament
P 1.5
P 1. 5
P 1.0
P 1. 0
P 0.5
P 0. 5
P 1.5/R P 0.5/R
P 0. 5/ R
P 1.5 PegIntron 1.5 micrograms/kg P 1.0 PegIntron 1.0 microgram/kg P 0.5 PegIntron 0.5 microgram/kg I Interferon alfa-2b 3 MIU P 1.5/R P 0.5/R I/ R * **
P 1. 5 PegIntron 1. 5 mikrogrammi/ kg P 1. 0 PegIntron 1. 0 mikrogramma/ kg P 0. 5 PegIntron 0. 5 mikrogramma/ kg I Interferon alfa- 2b 3 MIU P 1. 5/ R P 0. 5/ R I/ R * ** Tabella 6
Sustained response rates with PegIntron + ribavirin (by ribavirin dose, genotype and viral load)
I/ R Rati ta ’ risponsi sostnuti b 'PegIntron + ribavirin (bid- doża ta ’ ribavirin, ġenotip u viral load)
62 Genotype 2/3
Ġenotip 2/ 3
PegIntron (1.5 micrograms/kg) + ribavirin (800 mg) PegIntron (1.5 to 0.5 microgram/kg) + ribavirin (1,000/1,200 mg) Interferon alfa-2b (3 MIU) + ribavirin (1,000/1,200 mg)
PegIntron (1. 5 mikrogrammi/ kg) + ribavirin (800 mg) PegIntron (1. 5 to 0. 5 mikrogramma/ kg) + ribavirin (1, 000/ 1, 200 mg) Interferon alfa- 2b (3 MIU) + ribavirin (1, 000/ 1, 200 mg)
Genotype Viral response Sustained response Negative predictive value at week 12 1 Yes 75% (82/110) 71% (58/82) ---- No 25% (28/110) 0% (0/28) 100% 2 and 3 Yes 99% (213/215) 83% (177/213) ----
Ġinotip Rispons viroloġiku Rispons sostnut Valur negattiv ma ’ ġimgħa 12 imbassar 1 Iva 75% (82/ 110) 71% (58/ 82) ---- Le 25% (28/ 110) 0% (0/ 28) 100%
64 Table 9
Tabella 9
65 Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għall- kura mill- ġdid f’ Każijiet fejn il- Kura Qabel kienet falliet
SVR% (n/N) 99% CI
Response SVR% (n/ N) Week 12% 99% CI (n/ N)
23.0 (16 2/704)
23. 0 (162/ 704)
66 Overall, approximately 36% (821/2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ml).
B’ mod globali, madwar 36% (821/ 2, 286) tal- pazjenti kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jitkejlu mat- 12- il Ġimgħa ta ’ terapija imkejjla permezz ta ’ test ibbażat fuq riċerka (limitu li seta ’ jitkejjel 125 IU/ ml).
However, renal elimination may account for a minority (approximately 30%) of Peg Intron apparent clearance.
Madanakollu, l- eliminazzjoni mill- kliewi tista ’ tirrifletti ammont ċkejken (madwar 30%) tal- clearance apparenti ta ’ PegIntron.
67 for monotherapy should be reduced in patients with moderate or severe renal impairment (see sections 4.2 and 4.4).
Id- doża ta ’ PegIntron għal monoterapija għandha titnaqqas f’ pazjenti b’ indeboliment renali ħafif għal moderat (ara sezzjonijiet 4. 2 u 4. 4).
68 Water for injections.
Ilma għall- injezzjoni
The powder is contained in a 2 ml vial, Type I flint glass, with a butyl rubber stopper in an aluminium flip -off seal with a polypropylene bonnet.
It- trab jinżamm fi kunjett ta ’ 2 ml, ta ’ ħġieġ taż- żnied tat- Tip I, b’ tapp tal- lasktu tal- butyl b’ siġill ta ’ l - aluminium li jinfetaħ b’ saba ’ b’ għatu tal- polypropylene.
PegIntron 100 micrograms is supplied as:
PegIntron 100 mikrogrammi jiġi bħala:
PegIntron is supplied as a powder of peginterferon alfa-2b at a strength of 100 micrograms for single use.
6. 6 Prekawzjonijiet speċjali li għ andhom jittieħ du meta jintrema u għ al immaniġġar ieħ or PegIntron jiġi bħala trab ta ’ peginterferon alfa- 2b b’ qawwa ta ’ 100 mikrogrammi li jista ’ jintuża darba biss.
The reconstituted solution has a concentration of 100 micrograms/0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 100 mikrogrammi/ 0. 5 ml.
PegIntron 120 micrograms powder and solvent for solution for injection
PegIntron 120 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial of PegIntron, powder for solution for injection contains 120 micrograms of peginterferon alfa- 2b as measured on a protein basis.
Kull kunjett ta ’ PegIntron, trab għal soluzzjoni għall- injezzjoni fih 120 mikrogrammi ta ’ peginterferon alfa - 2b hekk kif imkejjel fuq bażi ta ’ proteina.
Each vial provides 120 micrograms/0.5 ml of peginterferon alfa-2b when reconstituted as recommended.
Kull kunjett jipprovdi 120 mikrogrammi/ 0. 5 ml ta ’ peginterferon alfa- 2b meta rikostitwit kif rakkomandat.
71 Combination therapy PegIntron 1.5 micrograms/kg/week in combination with ribavirin capsules.
Terapija konġunta PegIntron 1. 5 mikrogrammi/ kg/ ġimgħa flimkien ma 'kapsuli ta ’ ribavirin.
72 Duration of treatment - Retreatment Predictability of sustained virological response:
Kemm għandha ddum il- kura – Trattament mill- ġdid Kemm jista ’ jiġi mbassar r- rispons viroloġiku sostnut:
Vial/Pen Strength
Pinna/ Kunjett (μg/ 0. 5ml)
Administer Vial/Pen Once Weekly Strength
Darba fil - Pinna/ Kunjett Ġimgħa (μg/ 0. 5ml) (ml)
Administer Once Weekly
Darba fil - Ġimgħa (ml)
(μg/0.5ml)
50 * 50 * 50 * 50 50
(ml) (μg/0.5ml)
0. 15 50 0. 2 50 0. 25 50 0. 3 80 0. 4 80
50 * 50* 50* 50 50 50 80
0. 5 0. 4
73 Combination Therapy Dose Reduction Guidelines
Linji Gwida Dwar it- Tnaqqis fid- Doża tat- Terapija Kombinata
Strength
Kunjett/ Pinna (μg/ 0. 5 ml)
Once Weekly
Darba fil - Ġimgħa (ml)
74 Dose reduction for patients who use 0.5 μg/kg PegIntron monotherapy must be accomplished by reducing the prescribed volume by one-half.
Tnaqqis fid- doża għal pazjenti li jużaw il- monoterapija ta ’ PegIntron 0. 5 μg/ kg għandu jinkiseb billi jitnaqqas il- volum preskritt bin- nofs.
(μg/0.5ml)
Intenzjonat (μg)
76 Hydration:
Idratazzjoni:
77 Haematological abnormalities in HCV/HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with Peg Intron and ribavirin.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkollhom jittieħdu fl- istes ħin ma’ terapija HCV għall- għarfien u maniġġjar tat- tossiċitajiet speċifiċi għal kull prodott u l- potenzjal li jista ’ jkun hemm tossiċitajiet f ’ daqqa b’ PegIntron u ribavirin.
These findings may partly relate to improved metabolic capacity due to reduced hepatic inflammation in patients undergoing treatment with Peg Intron.
Dawn is- sejbiet jistgħu jgħinu xi ftit sabiex titjieb il- ħila metabolika minħabba tnaqqid fl- infjammazzjoni epatika f’ pazjenti li jkunu taħt kura b’ PegIntron.
79 childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Nisa li jista ’ jkollhom it- tfal u s- sieħba tagħhom għandhom jużaw kontraċezzjoni effettiva kull wieħed waqt il- kura u għal 4 xhur wara li tkun intemmet il- kura.
80 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Interstitial lung disease 81
Disturbi gastro- intestinali Komuni ħafna:
82 Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
Każijiet avversi kardjovaskulari (CVS), l- aktar arritmija, dehru li kellhom x’ jaqsmu l- aktar ma ’ mard pri - eżistenti CVS u ma ’ l- għotja ta ’ aġenti kardjotossiċi xi darba qabel (ara sezzjoni 4. 4).
Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with Peg Intron in combination with ribavirin.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkollhom jittieħdu fl- istes ħin ma ’ terapija HCV għall- għarfien u maniġġjar tat- tossiċitajiet speċifiċi għal kull prodott u l- potenzjal li jista ’ jkun hemm tossiċitajiet f’ daqqa b’ PegIntron f’ kombinazzjoni ma ’ ribavirin.
83 treatment and close observation of the patient are recommended in cases of overdose.
M’ hemm l- ebda antidotu speċifiku għal PegIntron; għalhekk, kura sintomatika o osservaz+zjoni mill- qrib tal- pazjent hija rakkomandata f’ każijiet ta ’ doża eċċessiva.
Following single doses of Peg Intron between 0.25 and 2.0 micrograms/kg/week, serum neopterin concentration was increased in a dose- related manner.
Wara dożi singoli ta ’ PegIntron ta ’ bejn 0. 25 u 2. 0 mikrogrammi/ kg/ ġimgħa, il- konċentrazzjoni ta ’ neopterin fis- serum żdiedet b’ mod li kien relatat mad- doża.
84 In the PegIntron combination trial, 1,530 naïve patients were treated for one year with one of the following combination regimens: • PegIntron (1.5 micrograms/kg/week) + ribavirin (800 mg/day), (n = 511). • PegIntron (1.5 micrograms/kg/week for one month followed by 0.5 microgram/kg/week for 11 months) + ribavirin (1,000/1,200 mg/day), (n = 514). • Interferon alfa-2b (3 MIU three times a week) + ribavirin (1,000/1,200 mg/day) (n = 505).
Fi prova fejn PegIntron intuża f’ kombinazzjoni, 1, 530 pazjent naïve ingħataw trattament għal sena b’ wieħed mill- korsijiet ikkumbinati li ġejjin: • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) + ribavirin (800 mg kuljum), (n = 511). • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwit 0. 5 mikrogrammi/ kg/ ġimgħa għal ħdax - il xahar) + ribavirin (1, 000/ 1, 200 mg kuljum), (n = 514). • Interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg kuljum) (n = 505).
Sustained virological response (% patients HCV negative PegIntron monotherapy
Reazzjoni viroloġika
85 Genotype 2/3
Ġenotip 2/ 3
The duration of thera py was 48 weeks with a follow-up period of 6 months except for patients infected with genotypes 2 or 3 and viral load < 800,000 IU/ml (Amplicor) who were treated for 24 weeks with a 6-month follow-up period.
It- tul tat- terapija kien 48 ġimgħa bi perijodu ta ’ follow- up ta ’ 6 xhur ħlief għall- pazjenti infettati b’ ġenotip 2 jew 3 u viral load < 800, 000 IU/ ml (Ampiclor) li kienu ikkurati għal 24 ġimgħa bi perijodu follow- up ta ’ 6 xhur.
87 Table 9
Tabella 9
Sustaine d virological response based on genotype after PegIntron in combination with Ribavirin in HCV/HIV Co-infected patients Study 11 Study 22 PegIntron Interferon PegIntron Interferon (100 or alfa-2b (1.5 µg/kg/ alfa-2b 150c µg/week) (3 MIU TIW) week) + (3 MIU TIW) + + ribavirin + ribavirin
Rispons viroloġiku sostnut ibbażat fuq il- ġenotip wara PegIntron f’ kombinazzjoni ma ’ Ribavirin f’ pazjenti infettati fl- istess ħin b’ HCV/ HIV Studju 11 Studju 22 PegIntron (100 jew Interferon 150c PegIntron Interferon alfa- 2b µg/ ġimgħa) + (3 MIU TIW) (1. 5 µg/ kg / alfa- 2b ribavirin + ribavirin ġimgħa) + (3 MIU TIW) + valur - ribavirin ribavirin valur - (800 - (800 - pb d a d 1, 200 mg) (800 mg) (800 mg) p 1, 200 mg)
MIU = million international units; TIW = three times a week. a: p value based on Cochran-Mantel Haenszel Chi square test. b: p value based on chi-square test. c: subjects < 75 kg received 100 µg/week PegIntron and subjects ≥ 75 kg received 150 µg/week PegIntron. d: ribavirin dosing was 800 mg for patients < 60 kg, 1,000 mg for patients 60-75 kg, and 1, 200 mg for patients > 75 kg.
MIU =miljun unitajiet internazzjonali; TIW = tlett darbiet fil- ġimgħa. a: valur- p ibbażat fuq it- test Cochran- Mantel Haenszel Chi square. b: valur- p ibbażat fuq it- test chi- square. c: individwi < 75 kg irċevew 100 µg/ ġimgħa PegIntron u individwi ≥ 75 kg irċevew 150 µg/ ġimgħa PegIntron. d: għall- pazjenti < 60 kg ingħataw dożi ta ’ 800 mg ribavirin, 1, 000 mg għall- pazjenti 60- 75 kg, u 1, 200 mg għall- pazjenti > 75 kg.
88 Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għall- kura mill- ġdid f’ Każijiet fejn il- Kura Qabel kienet falliet
73.0 (135/185) 6 4.6, 81.4
73. 0 (135/ 185) 64. 6, 81. 4
89 Overall, approximately 36% (821/2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ml).
B’ mod globali, madwar 36% (821/ 2, 286) tal- pazjenti kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jitkejlu mat- 12- il Ġimgħa ta ’ terapija imkejjla permezz ta ’ test ibbażat fuq riċerka (limitu li seta ’ jitkejjel 125 IU/ ml).
90 for monotherapy should be reduced in patients with moderate or severe renal impairment (see sections 4.2 and 4.4).
Id- doża ta ’ PegIntron għal monoterapija għandha titnaqqas f’ pazjenti b’ indeboliment renali ħafif għal moderat (ara sezzjonijiet 4. 2 u 4. 4).
91 Water for injections.
Ilma għall- injezzjoni
PegIntron 120 micrograms is supplied as:
PegIntron 120 mikrogrammi jiġi bħala:
PegIntron is supplied as a powder of peginterferon alfa-2b at a strength of 120 micrograms for single use.
6. 6 Prekawzjonijiet speċjali li għ andhom jittieħ du meta jintrema u għ al immaniġġar ieħ or PegIntron jiġi bħala trab ta ’ peginterferon alfa- 2b b’ qawwa ta ’ 120 mikrogrammi li jista ’ jintuża darba biss.
The reconstituted solution has a concentration of 120 micrograms/0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 120 mikrogrammi/ 0. 5 ml.
PegIntron 150 micrograms powder and solvent for solution for injection
PegIntron 150 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial of PegIntron, powder for solution for injection contains 150 micrograms of peginterferon alfa- 2b as measured on a protein basis.
Kull kunjett ta ’ PegIntron, trab għal soluzzjoni għall- injezzjoni fih 150 mikrogrammi ta ’ peginterferon alfa - 2b hekk kif imkejjel fuq bażi ta ’ proteina.
Each vial provides 150 micrograms/0.5 ml of peginterferon alfa-2b when reconstituted as recommended.
Kull kunjett jipprovdi 150 mikrogrammi/ 0. 5 ml ta ’ peginterferon alfa- 2b meta rikostitwit kif rakkomandat.
94 Combination therapy PegIntron 1.5 micrograms/kg/week in combination with ribavirin capsules.
Terapija konġunta PegIntron 1. 5 mikrogrammi/ kg/ ġimgħa flimkien ma 'kapsuli ta ’ ribavirin.
95 Duration of treatment - Retreatment Predictability of sustained virological response:
Kemm għandha ddum il- kura – Trattament mill- ġdid Kemm jista ’ jiġi mbassar r- rispons viroloġiku sostnut:
The lowest vial or pen strength available is 50 μg/ 0.5 ml; therefore for patients prescribed 0.5 μ g/ kg/week, doses must be adjusted by volume as shown in Table 2.
L- iktar qawwa baxxa disponibbli ta ’ kunjett jew pinna hija ta ’ 50 μg/ 0. 5 ml; għaldaqstant għal pazjenti li ġew mogħtija preskrizzjoni ta ’ 0. 5 μg/ kg/ ġimgħa, id- dożi għandhom jiġu regolati bil- volum kif muri fi Tabella 2.
96 Combination Therapy Dose Reduction Guidelines
Linji Gwida Dwar it- Tnaqqis fid- Doża tat- Terapija Kombinata
dose to one -half dose if:
għal nofs- doża biss jekk:
g/dl decrease in haemoglobin during any four week period during treatment (permanent dose reduction) -< 1.5 x 109/l -< 0.7 5 x 109/l 9
erba ’ ġimgħat waqt it- trattament (tnaqqis permanenti fid- doża)
-< 50 x 10 /l - -> 5 mg/dl -
> 5 mg/ dl -
97 Dose reduction for patients who use 0.5 μg/kg PegIntron monotherapy must be accomplished by reducing the prescribed volume by one-half.
Tnaqqis fid- doża għal pazjenti li jużaw il- monoterapija ta ’ PegIntron 0. 5 μg/ kg għandu jinkiseb billi jitnaqqas il- volum preskritt bin- nofs.
4.3 Contra indications
4. 3 Kontra- indikazzjonijiet
99 Hydration:
Idratazzjoni:
Discontinuation of Peg Intron should be considered in patients who develop new or worsening ophthalmological disorders.
F’ pazjenti illi jiżviluppaw mard f’ għajnejhom, jew li l- mard f’ għajnejhom imur għall- agħar, wieħed għandu jikkunsidra li PegIntron jitwaqqaf.
100 Haematological abnormalities in HCV/HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
102 childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Nisa li jista ’ jkollhom it- tfal u s- sieħba tagħhom għandhom jużaw kontraċezzjoni effettiva kull wieħed waqt il- kura u għal 4 xhur wara li tkun intemmet il- kura.
103 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Interstitial lung disease 104
Disturbi gastro- intestinali Komuni ħafna:
These adverse reactions were common (≥1/100 to < 1/10) in clinical trials in patients treated with Peg Intron monother apy.
Dawn ir- reazzjonijiet avversi kienu komuni (≥1/ 100 sa < 1/ 10) fi provi kliniċi f’ pazjenti kkurati b’ monoterapija b’ PegIntron.
105 Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
Każijiet avversi kardjovaskulari (CVS), l- aktar arritmija, dehru li kellhom x’ jaqsmu l- aktar ma ’ mard pri - eżistenti CVS u ma ’ l- għotja ta ’ aġenti kardjotossiċi xi darba qabel (ara sezzjoni 4. 4).
106 treatment and close observation of the patient are recommended in cases of overdose.
M’ hemm l- ebda antidotu speċifiku għal PegIntron; għalhekk, kura sintomatika o osservaz+zjoni mill- qrib tal- pazjent hija rakkomandata f’ każijiet ta ’ doża eċċessiva.
Subjects treated with Peg Intron showed mild dose-related elevations in body temperature.
Dawk illi kienu trattati b’ PegIntron urew zjieda żgħ ira fit- temperatura tal- ġisem li kienet konnessa mad- doża.
107 In the PegIntron combination trial, 1,530 naïve patients were treated for one year with one of the following combination regimens: • PegIntron (1.5 micrograms/kg/week) + ribavirin (800 mg/day), (n = 511). • PegIntron (1.5 micrograms/kg/week for one month followed by 0.5 microgram/kg/week for 11 months) + ribavirin (1,000/1,200 mg/day), (n = 514). • Interferon alfa-2b (3 MIU three times a week) + ribavirin (1,000/1,200 mg/day) (n = 505).
Fi prova fejn PegIntron intuża f’ kombinazzjoni, 1, 530 pazjent naïve ingħataw trattament għal sena b’ wieħed mill- korsijiet ikkumbinati li ġejjin: • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) + ribavirin (800 mg kuljum), (n = 511). • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwit 0. 5 mikrogrammi/ kg/ ġimgħa għal ħdax - il xahar) + ribavirin (1, 000/ 1, 200 mg kuljum), (n = 514). • Interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg kuljum) (n = 505).
Peg Intron + ribavirin
sostenuta (% ta ’ pazjenti negattivi għal HCV) Monoterapija b 'PegIntron PegIntron + ribavirin
108 Genotype 2/3
Ġenotip 2/ 3
Predictability of sustained response by viral response at week 12 and genotype *
Tbassir ta ’ rispons sostnut permezz ta ’ reazzjoni virali sat- tnax- il ġimgħa u ġenotip *
110 Table 9
Tabella 9
111 Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għall- kura mill- ġdid f’ Każijiet fejn il- Kura Qabel kienet falliet
67.9 (74/ 109)
67. 9 (74/ 109)
77.1 (185/2 40)
77. 1 (185/ 240)
112 Overall, approximately 36% (821/2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ml).
B’ mod globali, madwar 36% (821/ 2, 286) tal- pazjenti kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jitkejlu mat- 12- il Ġimgħa ta ’ terapija imkejjla permezz ta ’ test ibbażat fuq riċerka (limitu li seta ’ jitkejjel 125 IU/ ml).
Mean (SD) Peg Intron elimin ation half-life is approximately 40 hours (13.3 hours), with apparent clearance of 22.0 ml/hr·kg.
Il- half- life ta ’ Pegintron hija ta ’ madwar 40 siegħa (13. 3 siegħa) b’ rata ta ’ eliminazzjoni apparenti ta ’ 22. 0 ml/ hr· kg.
113 for monotherapy should be reduced in patients with moderate or severe renal impairment (see sections 4.2 and 4.4).
Id- doża ta ’ PegIntron għal monoterapija għandha titnaqqas f’ pazjenti b’ indeboliment renali ħafif għal moderat (ara sezzjonijiet 4. 2 u 4. 4).
114 Water for injections.
Ilma għall- injezzjoni
PegIntron 150 micrograms is supplied as:
PegIntron 150 mikrogrammi jiġi bħala:
PegIntron is supplied as a powder of peginterferon alfa-2b at a strength of 150 micrograms for single use.
6. 6 Prekawzjonijiet speċjali li għ andhom jittieħ du meta jintrema u għ al immaniġġar ieħ or PegIntron jiġi bħala trab ta ’ peginterferon alfa- 2b b’ qawwa ta ’ 150 mikrogrammi li jista ’ jintuża darba biss.
The reconstituted solution has a concentration of 150 micrograms/0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 150 mikrogrammi/ 0. 5 ml.
PegIntron 50 micrograms, powder and solvent for solution for injection in pre-filled pen
PegIntron 50 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest.
Each pre-filled pen of PegIntron 50 micrograms contains a sufficient amount of peginterferon alfa-2b as measured on a protein basis in a powder for solution for injection, and the corresponding amount of solvent, to provide 50 micrograms in 0.5 ml of peginterferon alfa-2b when reconstituted as recommended.
Kull pinna mimlija għal lest ta ’ PegIntron 50 mikrogramma fihom biżżejjed peginterferon alfa- 2b hekk kif imkejjel fuq bażi ta ’ proteina f’ trab għal soluzzjoni għall- injezzjoni, u l- ammont korrispondenti ta ’ solvent, sabiex jipprovdi 50 mikrogramma f’ 0. 5 ml ta ’ peginterferon alfa- 2b meta rikostitwit kif rakkomandat.
Powder and solvent for solution for injection in pre-filled pen White powder.
Trab u solvent għal soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest Trab abjad.
117 Combination therapy PegIntron 1.5 micrograms/kg/week in combination with ribavirin capsules.
Terapija konġunta PegIntron 1. 5 mikrogrammi/ kg/ ġimgħa flimkien ma 'kapsuli ta ’ ribavirin.
118 Duration of treatment - Retreatment Predictability of sustained virological response:
Kemm għandha ddum il- kura – Trattament mill- ġdid Kemm jista ’ jiġi mbassar r- rispons viroloġiku sostnut:
PegIntron monotherapy As monotherapy the PegIntron regimen is 0.5 or 1.0 microgram/k g/week.
Monoterapija b’ PegIntron Bħala monoterapija l- kors ta ’ PegIntron huwa ta ’ 0. 5 jew 1. 0 mikrogramma/ kg/ ġimgħa.
119 Combination Therapy Dose Reduction Guidelines
Linji Gwida Dwar it- Tnaqqis fid- Doża tat- Terapija Kombinata
Platelets Bilirubin – direct Bilirubin – indirect
Bilirubin – dirett
120 Dose reduction for patients who use 0.5 μg/kg PegIntron monotherapy must be accomplished by reducing the prescribed volume by one-half.
Tnaqqis fid- doża għal pazjenti li jużaw il- monoterapija ta ’ PegIntron 0. 5 μg/ kg għandu jinkiseb billi jitnaqqas il- volum preskritt bin- nofs.
There are no apparent age -related effects on the pharmacokinetics of PegIntron.
Jidher li ma hemm l- ebda effetti relatati ma ’ l- età fuq il- farmakokinetiċi ta ’ PegIntron.
in the previous six months (see section 4.4); 121
sitt xhur ta ’ qabel (ara sezzjoni 4. 4);
122 Hydration:
Idratazzjoni:
Periodic visual examinations are recommended during Peg Intron therapy, particularly in patients with disorders that may be associated with retinopathy, such as diabetes mellitus or hypertension.
Huwa rakkomandat illi jsiru eżamijiet ta ’ l- għajnejn kull tant żmien waqt li qed jingħata PegIntron, l- aktar f’ dawk il- pazjenti b’ mard illi jista ’ jkun konness mar - retinopatija, bħal zokkor għoli fid- demm jew pressjoni għolja.
123 Haematological abnormalities in HCV/HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
125 childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Nisa li jista ’ jkollhom it- tfal u s- sieħba tagħhom għandhom jużaw kontraċezzjoni effettiva kull wieħed waqt il- kura u għal 4 xhur wara li tkun intemmet il- kura.
126 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Interstitial lung disease 127
Disturbi gastro- intestinali Komuni ħafna:
128 Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
Każijiet avversi kardjovaskulari (CVS), l- aktar arritmija, dehru li kellhom x’ jaqsmu l- aktar ma ’ mard pri - eżistenti CVS u ma ’ l- għotja ta ’ aġenti kardjotossiċi xi darba qabel (ara sezzjoni 4. 4).
HCV/HIV co-infected patients For HCV/HIV co-infected patients receiving Peg Intron in combination with ribavirin, other undesirable effects (that were not reported in mono-infected patients) which have been reported in the larger studies with a frequency > 5% were: oral candidiasis (14%), lipodystrophy acquired (13%), CD4 lymphocytes decreased (8%), appetite decreased (8%), gamma-glutamyltransferase increased (9%), back pain (5%), blood amylase increased (6%), blood lactic acid increased (5%), cytolytic hepatitis (6%), lipase increased (6%) and pain in limb (6%).
Pazjenti infettati fl- istess ħin b’ HCV/ HIV Għall- pazjenti infettati fl- istess ħin b’ HCV/ HIV li qed jirċievu PegIntron f’ kombinazzjoni ma ’ ribavirin, effetti oħra mhux mixtieqa (li ma kienux irrappurtati f’ pazjenti b’ infezzjoni waħda) li kienu irrappurtati fl - istudji b’ frekwenza ta ’ > 5% kienu: kandidijażi orali (14%), lipodistrofija akkwiżita (13%), tnaqqis fil - limfoċiti CD4 (8%), tnaqqis fl- aptit (8%), żieda tal- gamma- glutamyltransferase (9%), uġigħ fid- dahar (5%), żieda ta ’ l- amylase fid- demm (6%), żieda tal- lactic acid fid- demm (5%), epatite ċitolitika (6%), żieda tal - lipase (6%) u uġigħ fir- riġel (6%).
The use of Peg Intron in combination with ribavirin had no observable negative impact on the control of HIV viraemia during therapy or follow-up.
L- użu ta ’ PegIntron f’ kombinazzjoni ma ’ ribavirin ma deherx li kellu impatt negattiv fuq il- kontroll ta ’ virimja bl- HIV waqt it- terapija jew fiż - żmien ta ’ follow- up.
129 treatment and close observation of the patient are recommended in cases of overdose.
M’ hemm l- ebda antidotu speċifiku għal PegIntron; għalhekk, kura sintomatika o osservaz+zjoni mill- qrib tal- pazjent hija rakkomandata f’ każijiet ta ’ doża eċċessiva.
Peg Intron PegIntron pharmacodynamics were assessed in a rising single-dose trial in healthy subjects by examining changes in oral temperature, concentrations of effector proteins such as serum neopterin and 2’5’- oligoadenylate syn thetase (2’5’-OAS), as well as white cell and neutrophil counts.
PegIntron Il- farmakodinamiċi ta ’ PegIntron kienu mistħarrġa fi prova ta ’ doża waħda li tiżdied f’ suġġetti b’ saħħithom billi ġew mkejla bidliet fit- temperatura orali, konċentrazzjonijiet ta ’ proteini effetturi bħalma huma neopterin tas- serum u 2’ 5 ’ - oligoadenylate synthetase (2’ 5 ’ - OAS), kif ukoll in- numru ta ’ ċelluli bojod u tan- newtrofili.
Following single doses of PegIntron between 0.25 and 2.0 micrograms/kg/week, serum neopterin concentration was increased in a dose-related manner.
Wara dożi singoli ta ’ PegIntron ta ’ bejn 0. 25 u 2. 0 mikrogrammi/ kg/ ġimgħa, il- konċentrazzjoni ta ’ neopterin fis- serum żdiedet b’ mod li kien relatat mad- doża.
130 In the PegIntron combination trial, 1,530 naïve patients were treated for one year with one of the following combination regimens: • PegIntron (1.5 micrograms/kg/week) + ribavirin (800 mg/day), (n = 511). • PegIntron (1.5 micrograms/kg/week for one month followed by 0.5 microgram/kg/week for 11 months) + ribavirin (1,000/1,200 mg/day), (n = 514). • Interferon alfa-2b (3 MIU three times a week) + ribavirin (1,000/1,200 mg/day) (n = 505).
Fi prova fejn PegIntron intuża f’ kombinazzjoni, 1, 530 pazjent naïve ingħataw trattament għal sena b’ wieħed mill- korsijiet ikkumbinati li ġejjin: • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) + ribavirin (800 mg kuljum), (n = 511). • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwit 0. 5 mikrogrammi/ kg/ ġimgħa għal ħdax - il xahar) + ribavirin (1, 000/ 1, 200 mg kuljum), (n = 514). • Interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg kuljum) (n = 505).
Sustained virological response (% patients HCV negative) Peg Intron monotherapy
Reazzjoni viroloġika
I p = 0.0143 P 1.5/ R vs.
I p = 0. 0143 P 1. 5/ R vs.
Viral response Sustained response Negative predictive value at week 12 1 Yes 75% (82/110) 71% (58/82) ---- No 25% (28/ 110) 0% (0/28) 100%
Ġinotip Rispons viroloġiku Rispons sostnut Valur negattiv ma ’ ġimgħa 12 imbassar 1 Iva 75% (82/ 110) 71% (58/ 82) ---- Le 25% (28/ 110) 0% (0/ 28) 100%
Patients were randomized to receive either PegIntron (1.5 µg/kg/week) plus ribavirin (800 mg/day) or interferon alfa-2b (3 MIU TIW) plus ribavirin (800 mg/day) for 48 weeks with a follow-u p period of 6 months.
Il- pazjenti kienu randomized sabiex jirċievu PegIntron (1. 5 µg/ kg/ ġimgħa) ma ’ ribavirin (800 mg/ jum) jew interferon alfa- 2b (3 MIU TIW) ma ’ ribavirin (800 mg/ jum) għal 48 ġimgħa b’ perijodu ta ’ follow- up ta ’ 6 xhur.
Patients were randomized to receive either PegIntron (100 or 150 µg /week based on weight) plus ribavirin (800- 1,200 mg/day based on weight) or interferon alfa-2b (3 MIU TIW) plus ribavirin (800-1,200 mg/day based on weight).
Il- pazjenti kienu randomized biex jirċievu PegIntron (100 jew 150 µg/ ġimgħa skond il- piż) ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż) jew interferon alfa- 2b (3 MIU TIW) ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż).
133 Table 9
Tabella 9
134 Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għall- kura mill- ġdid f’ Każijiet fejn il- Kura Qabel kienet falliet
135 Overall, approximately 36% (821/2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ml).
B’ mod globali, madwar 36% (821/ 2, 286) tal- pazjenti kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jitkejlu mat- 12- il Ġimgħa ta ’ terapija imkejjla permezz ta ’ test ibbażat fuq riċerka (limitu li seta ’ jitkejjel 125 IU/ ml).
136 for monotherapy should be reduced in patients with moderate or severe renal impairment (see sections 4.2 and 4.4).
Id- doża ta ’ PegIntron għal monoterapija għandha titnaqqas f’ pazjenti b’ indeboliment renali ħafif għal moderat (ara sezzjonijiet 4. 2 u 4. 4).
1 37 Water for injections.
Ilma għall- injezzjoni
Deliverable volume from pen = 0.5 ml.
Volum li jista ’ jingħata mill- pinna = 0. 5 ml.
Do not freeze.
Tgħamlux fi friża.
The powder and solvent are both contained in a two-chamber cartridge, Type I flint glass, separated by a bromobutyl rubber plunger.
Glass taż- żnied tat- tip I, separat bi plunġer tal- lasktu tal- bromobutyl.
The cartridge is sealed at one end with a polypropylene cap containing a bromobutyl rubber liner and at the other end by a bromobutyl rubber plunger.
L- iskartoċċ issiġillat minn naħa waħda b’ għatu tal- polypropylene b’ kisja tal- lasktu tal- bromobutyl u minn naħa l- oħra bi planġer tal- bromobutyl.
- 1 pen containing powder and solvent for solution for injection, 1 injection needle and 2 cleansing
- pinna 1 li jkun fiha trab u solvent għal soluzzjoni għall- injezzjoni, labra 1 ta ’ l- injezzjoni u 2 biċċiet għat -
swabs;
tindif
- 4 pens containing powder and solvent for solution for injection, 4 injection needles and 8 cleansing
- 4 pinnen li jkun fihom trab u solvent għal soluzzjoni għall- injezzjoni, 4 labar ta ’ l- injezzjoni u 8 biċċiet
swabs;
għat- tindif
- 6 pens containing powder and solvent for solution for injection, 6 injection needles
- 6 pinnen li jkun fihom trab u solvent għal soluzzjoni għall- injezzjoni, 6 labar ta ’ l- injezzjoni u 12- il biċċa
and 12 cleansing swabs;
għat- tindif
- 12 pens containing powder and solvent for solution for injection, 12 injection needles
- 12- il pinna li jkun fiha trab u solvent għal soluzzjoni għall- injezzjoni, 12- il labra ta ’ l- injezzjoni u 24 biċċa
and 24 cleansing swabs.
għat- tindif
6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għ andhom jittieħ du meta jintrema u għ al immaniġġar ieħ or
PegIntron pre-filled pen contains a powder of peginterferon alfa-2b and a solvent for solution at a strength of 50 micrograms for single use.
Il- pinna PegIntron mimlija għal- lest tiġi bħala trab ta ’ peginterferon alfa- 2b u solvent għal soluzzjoni b’ qawwa ta ’ 50 mikrogrammi li jista ’ jintuża darba biss.
Each pen is reconstituted with the solvent provided in the two-chamber cartridge (water for injections) for administration of up to 0.5 ml of solution.
Kull pinna tiġi rikostitwita bis- solvent li jkun hemm magħha l- iskartoċċ b’ żewġ kavitajiet (ilma għall- injezzjonijiet) biex tingħata sa 0. 5 ml ta ’ soluzzjoni.
Therefore, each pen contains an excess amount of solvent and PegIntron powder to ensure delivery of the labelled dose in 0.5 ml of PegIntron, solution for injection.
Għaldaqstant, kull pinna fiha ammont żejjed ta ’ solvent u trab ta ’ PegIntron sabiex jiġi żgurat l- għoti tad- doża msemmija fuq it- tikketta ġo 0. 5 ml ta ’ PegIntron, soluzzjoni għall- injezzjoni.
The reconstituted solution has a concentration of 50 micrograms in 0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 50 mikrogrammi/ 0. 5 ml.
PegIntron is injected subcutaneously after reconstituting the powder as instructed, attaching an injection needle and setting the prescribed dose.
PegIntron jiġi injettat taħt il- ġilda wara li jkun rikostitwit it- trab kif hemm fl- istruzzjonijiet, billi twaħħal labra ta ’ l- injezzjoni u tirregola d- doża ordnata.
A complete and illustrated set of instructions is provided in the Annex to the Package Leaflet.
Sett ta ’ istruzzjonijiet komplet jiġi ma ’ l- Anness tal- Fuljett ta ’ Tagħrif.
Remove PegIntron pre-filled pen from the refrigerator before administration to allow the solvent to reach
Neħħi l- pinna mimlija għal- lest ta ’ PegIntron mill- friġġ qabel l- għotja sabiex tħalli s- solvent jilħaq it - temperatura tal- kamra (mhux aktar minn 25ºC).
Do not use if discolouration or particulate matter is present.
Tużax jekk ikun hemm bidla fil- kulur.
After administering the dose, discard the PegIntron pre- filled pen and any unused solution contained in it.
Wara li tingħata d- doża, armi l- pinna mimlija għal- lest ta ’ PegIntron u kwalunkwe materjal li jkun fiha.
PegIntron 80 micrograms, powder and solvent for solution for injection in pre-filled pen
PegIntron 80 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest.
Each pre-filled pen of PegIntron 80 micrograms contains a sufficient amount of peginterferon alfa-2b as measured on a protein basis in a powder for solution for injection, and the corresponding amount of solvent, to provide 80 micrograms in 0.5 ml of peginterferon alfa-2b when reconstituted as recommended.
Kull pinna mimlija għal lest ta ’ PegIntron 80 mikrogramma fihom biżżejjed peginterferon alfa- 2b hekk kif imkejjel fuq bażi ta ’ proteina f’ trab għal soluzzjoni għall- injezzjoni, u l- ammont korrispondenti ta ’ solvent, sabiex jipprovdi 80 mikrogramma f’ 0. 5 ml ta ’ peginterferon alfa- 2b meta rikostitwit kif rakkomandat.
140 Combination therapy PegIntron 1.5 micrograms/kg/week in combination with ribavirin capsules.
Terapija konġunta PegIntron 1. 5 mikrogrammi/ kg/ ġimgħa flimkien ma 'kapsuli ta ’ ribavirin.
(μg/ 0.5ml)
Kuljum (mg)
141 Duration of treatment - Retreatment Predictability of sustained virological response:
Kemm għandha ddum il- kura – Trattament mill- ġdid Kemm jista ’ jiġi mbassar r- rispons viroloġiku sostnut:
142 Combination Therapy Dose Reduction Guidelines
Linji Gwida Dwar it- Tnaqqis fid- Doża tat- Terapija Kombinata
143 Dose reduction for patients who use 0.5 μg/kg PegIntron monotherapy must be accomplished by reducing the prescribed volume by one-half.
Tnaqqis fid- doża għal pazjenti li jużaw il- monoterapija ta ’ PegIntron 0. 5 μg/ kg għandu jinkiseb billi jitnaqqas il- volum preskritt bin- nofs.
Data from elderly patients treated with a s ingle dose of PegIntron suggest no alteration in PegIntron dose is necessary based on age (see section 5.2).
Informazzjoni minn pazjenti anzjani li ngħataw doża waħda ta ’ PegIntron tissuġġerixxi li m’ hemmx bżonn ta ’ tibdil fid- doża minħabba l- età (ara sezzjoni 5. 2).
in the previous six months (see section 4.4); 144
sitt xhur ta ’ qabel (ara sezzjoni 4. 4);
145 Hydration:
Idratazzjoni:
146 Haematological abnormalities in HCV/HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
148 childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Nisa li jista ’ jkollhom it- tfal u s- sieħba tagħhom għandhom jużaw kontraċezzjoni effettiva kull wieħed waqt il- kura u għal 4 xhur wara li tkun intemmet il- kura.
149 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Interstitial lung disease 150
Disturbi gastro- intestinali Komuni ħafna:
151 Cardiovascular (CVS) adverse events, particularly arrhythmia, appeared to be correlated mostly with pre-existing CVS disease and prior therapy with cardiotoxic agents (see section 4.4).
Każijiet avversi kardjovaskulari (CVS), l- aktar arritmija, dehru li kellhom x’ jaqsmu l- aktar ma ’ mard pri - eżistenti CVS u ma ’ l- għotja ta ’ aġenti kardjotossiċi xi darba qabel (ara sezzjoni 4. 4).
Peg Intron PegIntron pharmacodynamics were assessed in a rising single-dose trial in healthy subjects by examining changes in oral temperature, concentrations of effector proteins such as serum neopterin and 2’5’- oligoadenylate synthetase (2’5’-OAS), as well as white cell and neutrophil counts.
PegIntron Il- farmakodinamiċi ta ’ PegIntron kienu mistħarrġa fi prova ta ’ doża waħda li tiżdied f’ suġġetti b’ saħħithom billi ġew mkejla bidliet fit- temperatura orali, konċentrazzjonijiet ta ’ proteini effetturi bħalma huma neopterin tas- serum u 2’ 5 ’ - oligoadenylate synthetase (2’ 5 ’ - OAS), kif ukoll in- numru ta ’ ċelluli bojod u tan- newtrofili.
Following single doses of Peg Intron between 0.25 and 2.0 micrograms/kg/week, serum neopterin concentration was increased in a dose-related manner.
Wara dożi singoli ta ’ PegIntron ta ’ bejn 0. 25 u 2. 0 mikrogrammi/ kg/ ġimgħa, il- konċentrazzjoni ta ’ neopterin fis- serum żdiedet b’ mod li kien relatat mad- doża.
153 following combination regimens: • PegIntron (1.5 micrograms/kg/week) + ribavirin (800 mg/day), (n = 511). • PegIntron (1.5 micrograms/kg/week for one month followed by 0.5 microgram/kg/week for 11 months) + ribavirin (1,000/1,200 mg/day), (n = 514). • Interferon alfa-2b (3 MIU three times a week) + ribavirin (1,000/1,200 mg/day) (n = 505).
Fi prova fejn PegIntron intuża f’ kombinazzjoni, 1, 530 pazjent naïve ingħataw trattament għal sena b’ wieħed mill- korsijiet ikkumbinati li ġejjin: • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa) + ribavirin (800 mg kuljum), (n = 511). • PegIntron (1. 5 mikrogrammi/ kg/ ġimgħa għal xahar segwit 0. 5 mikrogrammi/ kg/ ġimgħa għal ħdax - il xahar) + ribavirin (1, 000/ 1, 200 mg kuljum), (n = 514). • Interferon alfa- 2b (3 MIU tlett darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg kuljum) (n = 505).
P 0.5/R I/R
P 1. 5/ R P 0. 5/ R I/ R
PegIntron (1.5 to 0.5 microgram/kg) + ribavirin (1,000/1,200 mg) Interferon alfa-2b (3 MIU) + ribavirin (1,000/1,200 mg)
PegIntron (1. 5 mikrogrammi/ kg) + ribavirin (800 mg) PegIntron (1. 5 to 0. 5 mikrogramma/ kg) + ribavirin (1, 000/ 1, 200 mg) Interferon alfa- 2b (3 MIU) + ribavirin (1, 000/ 1, 200 mg)
In a separate trial, 224 patients with genotype 2 or 3 received PegIntron, 1.5 microgram/kg subcutaneously, once weekly, in combination with ribavirin 800 mg –1,400 mg p.o. for 6 months (based on body weight, only three patients weighing > 105 kg, received the 1,400 mg dose, which has not yet been validated) (Table 7).
Fi prova separata, 224 pazjent b’ ġenotip 2 jew 3 irċevew PegIntron, 1. 5 mikrogrammi/ kg minn taħt il - ġilda, darba fil- ġimgħa, f’ kombinazzjoni ma ’ ribavirin 800 mg- 1, 400 mg p. o. għal 6 xhur (ibbażat fuq il - piż tal- ġisem, tlett pazjenti biss kienu jiżnu > 105 kg, irċevew doża ta ’ 1, 400 mg) (Tabella 7).
Patients were ran domized to receive either PegIntron (100 or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or interferon alfa-2b (3 MIU TIW) plus ribavirin (800-1,200 mg/day based on weight).
Il- pazjenti kienu randomized biex jirċievu PegIntron (100 jew 150 µg/ ġimgħa skond il- piż) ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż) jew interferon alfa- 2b (3 MIU TIW) ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż).
156 Table 9
Tabella 9
157 Table 10 Rates of Response to retreatment in prior treatment failures
Tabella 10 Rati ta ’ Rispons għall- kura mill- ġdid f’ Każijiet fejn il- Kura Qabel kienet falliet
1 4.6 (270/1,846) 12.5, 16.7
14. 6 (270/ 1, 846 12. 5, 16. 7
158 Overall, approximately 36% (821/2,286) of patients had undetectable plasma HCV-RNA levels at Week 12 of therapy measured using a research-based test (limit of detection 125 IU/ml).
B’ mod globali, madwar 36% (821/ 2, 286) tal- pazjenti kellhom livelli ta ’ HCV- RNA fil- plażma li ma setgħux jitkejlu mat- 12- il Ġimgħa ta ’ terapija imkejjla permezz ta ’ test ibbażat fuq riċerka (limitu li seta ’ jitkejjel 125 IU/ ml).
159 for monotherapy should be reduced in patients with moderate or severe renal impairment (see sections 4.2 and 4.4).
Id- doża ta ’ PegIntron għal monoterapija għandha titnaqqas f’ pazjenti b’ indeboliment renali ħafif għal moderat (ara sezzjonijiet 4. 2 u 4. 4).
160 Water for injections.
Ilma għall- injezzjoni
The powder and solvent are both contained in a two -chamber cartridge, Type I flint glass, separated by a bromobutyl rubber plunger.
Glass taż- żnied tat- tip I, separat bi plunġer tal- lasktu tal- bromobutyl.
PegIntron pre-filled pen contains a powder of peginterferon alfa-2b and a solvent for solution at a strength of 80 micrograms for single use.
Il- pinna PegIntron mimlija għal- lest tiġi bħala trab ta ’ peginterferon alfa- 2b u solvent għal soluzzjoni b’ qawwa ta ’ 80 mikrogrammi li jista ’ jintuża darba biss.
The reconstituted solution has a concentration of 80 micrograms in 0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 80 mikrogrammi/ 0. 5 ml.
PegIntron 100 micrograms, powder and solvent for solution for injection in pre-filled pen
PegIntron 100 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni f’ pinna mimlija għal- lest.