qanastek/EMEA-V3 huggingface dataset:
20 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).
In this subgroup, there was a 56% (463/823) sustained virological response rate.
F’ dan is- sottogrupp, kien hemm rata ta ’ rispons virloġiku sostnut ta ’ 56% (463/ 823).
For patients with prior failure on therapy with nonpegylated interferon or pegylated interferon and negative at Week 12, the sustained response rates were 59% and 50%, respectively.
Għall- pazjenti li kienu fallew għat- terapija li kienet ingħatat qabel b’ interferon mhux pegilat jew interferon pegilat u negattivi ma ’ Ġimgħa 12, it- rati ta ’ rispons sostnut kienu 59% u 50%, rispettivament.
Among 480 patients with > 2 log viral reduction but detectable virus at Week 12, altogether 188 patients continued therapy.
Fost 480 pazjent b ’ > 2 log tat- tnaqqis virali iżda b’ ammont ta ’ vajrus li jista ’ jiġi imkejjel ma ’ Ġimgħa 12, b’ kollox 188 pazjent komplew it- terapija.
In those patients the SVR was 12%.
F’ dawk il- pazjenti, l- SVR kien 12%.
Non-responders to prior therapy with pegylated interferon alpha/ribavirin were less likely to achieve a Week 12 response to retreatment than non-responders to nonpegylated interferon alpha/ribavirin (12.4% vs.
Dawk li ma kellhomx rispons għat- terapija li ngħatat qabel b’ interferon alpha pegilat/ ribavirin kellhom anqas ċans li jiksbu rispons f’ Ġimgħa 12 għall- kura mill- ġdid minn dawk li ma kellhomx rispons għal interferon alpha mhux pegilat/ ribavirin (12% vs 28. 6%).
However, if a Week 12 response was achieved, there was little difference in SVR regardless of prior treatment or prior response.
Madankollu, jekk inkiseb rispons f’ ġimgħa 12, kien hemm differenza żgħira fl- SVR irrispettivament minn jekk kienetx ingħatat kura minn qabel jew jekk kienx hemm rispons qabel.
Long-Term efficacy data A large long-term follow-up study enrolled 567 patients after treatment in a prior study with PegIntron (with or without ribavirin).
Dejta dwar l- effikaċja fuq medda twila ta ’ żmien Studju kbir ta ’ follow- up fuq medda twila ta ’ żmien ingaġġa 567 pazjent wara kura fi studju li sar qabel b’ PegIntron (b’ ribavirin jew mingħajru).
The purpose of the study was to evaluate the durability of sustained virologic response (SVR) and assess the impact of continued viral negativity on clinical outcomes.
L- għan ta ’ l- istudju kienu li jiġi evalwat kemm idum ir- rispons viroloġiku sostnut (SVR) u jiġi stmat l- impatt ta ’ negattività virali kontinwa fuq ir- riżultati kliniċi.
327 patients completed at least 5 years of long-term follow-up and only 3 out of 366 sustained responders relapsed during the study.
327 pazjent lestew mill- anqas 5 snin ta ’ follow- up fuq medda twila ta ’ żmien u 3 biss minn 366 pazjent li kellhom rispons viroloġiku sostnut irkadew waqt l- istudju.
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 99% (95% CI:
L- istima Kaplan- Meier għal rispons viroloġiku sostnut fuq medda ta ’ 5 snin għall- pazjenti kollha hija 99% (95% CI:
SVR after treatment of chronic HCV with PegIntron (with or without ribavirin) results in long-term clearance of the virus providing resolution of the hepatic infection and clinical “cure” from chronic HCV.
SVR wara kura ta ’ HCV kronika b’ PegIntron (b’ ribavirin jew mingħajru) twassal għal tneħħija fit- tul tal- virus u b’ hekk tfejjaq l- infezzjoni epatika u “ fejqan ” kliniku minn HCV kroniku.
However, this does not preclude the occurrence of hepatic events in patients with cirrhosis (including hepatocarcinoma).
Madankollu dan ma jeskludix li jkun hemm każijiet epatiċi f’ pazjenti b’ ċirrożi (inkluża epatokarċinoma).
PegIntron is a well characterized polyethylene glycol-modified (“pegylated”) derivative of interferon alfa-2b and is predominantly composed of monopegylated species.
PegIntron huwa derivattiv modifikat ta ’ polyethylene glycol (“ pegylated ”) b' karatteristiċi mfissra tajjeb ta ’ interferon alfa- 2b u huwa magħmul prinċipalment minn speċi monopegylated.
The plasma half-life of PegIntron is prolonged compared with non-pegylated interferon alfa-2b.
Il- half- life ta ’ PegIntron fil - plażma hija mtawwla meta ’ mqabbla ma ’ interferon alfa- 2b mhux pegylated.
PegIntron has a potential to depegylate to free interferon alfa-2b.
PegIntron jista ’ jitlef il - pegylate biex isir interferon alfa- 2b liberu.
The biologic activity of the pegylated isomers is qualitatively similar, but weaker than free interferon alfa-2b.
L- attività bijoloġika ta ’ l- iżomeri bil- pegylate hija b' mod kwalitattiv l- istess, iżda aktar dgħajfa minn ta ’ interferon alfa- 2b liberu.
Following subcutaneous administration, maximal serum concentrations occur between 15-44 hours post-dose, and are sustained for up to 48-72 hours post-dose.
Wara li jingħata taħt il- ġilda, l- ogħla konċentrazzjonijiet fis- serum jintlaħqu bejn 15 u 44 siegħa wara d- doża, u huma sostnuti l- aktar għ al 48- 72 siegħa wara d- doża.
PegIntron Cmax and AUC measurements increase in a dose-related manner.
Is- Cmax u l- AUC ta ’ PegIntron jogħlew b’ mod relatat mad- doża.
Mean apparent volume of distribution is 0.99 l/kg.
Il- volum tad- distribuzzjoni medju apparenti huwa ta ’ 0. 99 l/ kg.
Upon multiple dosing, there is an accumulation of immunoreactive interferons.
Meta jingħataw ħafna dożi, hemm akkumulazzjoni ta ’ interferoni immunoreattivi.
There is, however, only a modest increase in biologic activity as measured by a bioassay.
Madankollu, hemm biss żjieda żgħira fl- attività bijoloġika meta mkejla b’ assay bijoloġiku.
Mean (SD) PegIntron elimination 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.
The mechanisms involved in clearance of interferons in man have not yet been fully elucidated.
Il- mekkaniżmi involuti fir- rata ta ’ eliminazzjoni ta ’ l- interferoni fil- bniedem għadhom ma ġewx iċċarati għal kollox.
However, renal elimination may account for a minority (approximately 30%) of PegIntron apparent clearance.
Madanakollu, l- eliminazzjoni mill- kliewi tista ’ tirrifletti ammont ċkejken (madwar 30%) tal- clearance apparenti ta ’ PegIntron.
Renal function:
Funzjoni tal- kliewi:
Renal clearance appears to account for 30% of total clearance of Peg Intron.
Jidher illi l- clearance mill- kliewi hija responsabbli għal 30% tar- rata kollha ta ’ eliminazzjoni ta ’ PegIntron.
In a single dose study (1.0 microgram/kg) in patients with impaired renal function, Cmax, AUC, and half- life increased in relation to the degree of renal impairment.
Fi studju fejn ingħatat doża waħda (1. 0 mikrogramma/ kg) lil pazjenti b’ indeboliment tal- kliewi, Cmax, AUC, il- half- life żdiedet b’ mod proporzjonali mal- livell ta ’ indeboliment tal- kliewi.
Following multiple dosing of PegIntron (1.0 microgram/kg subcutaneously administered every week for four weeks) the clearance of PegIntron is reduced by a mean of 17% in patients with moderate renal impairment (creatinine clearance 30-49 ml/minute) and by a mean of 44% in patients with severe renal impairment (creatinine clearance 15-29 ml/minute) compared to subjects with normal renal function.
Wara li ngħataw ħafna dożi ta ’ PegIntron (1. 0 mikrogramma/ kg minn taħt il- ġilda kull ġimgħa għal erba ’ ġimgħat) it- tneħħija ta ’ PegIntron tnaqqset b’ medja ta ’ 17% f’ pazjenti b’ indeboliment renali moderat (tneħħija tal- krejatinina 30- 49 ml/ min) u b’ medja ta ’ 44% f’ pazjenti b’ indeboliment renali sever (tneħħija tal- krejatinina 15- 29 ml/ minuta) mqabbel ma ’ individwi b’ funzjoni renali normali.
The dose of PegIntron
Ibbażat minn dejta b’ doża waħda, it- tneħħija kienet simili f’ pazjenti b’ indeboliment renali sever li ma kienux fuq dijaliżi u f’ pazjenti li kienu qed jirċievu emodijaliżi.
21 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).
Patients with creatinine clearance < 50 ml/minute must not be treated with PegIntron in combination with ribavirin (see section 4.3).
Pazjenti bi tneħħija tal - krejatinina < 50 ml/ minuta m’ għandhom ikunu ikkurati bi PegIntron ikkombinat ma’ ribavirin (ara sezzjoni 4. 3).
Because of marked inter-subject variability in interferon pharmacokinetics, it is recommended that patients with severe renal impairment be closely monitored during treatment with PegIntron (see section 4.2)
Peress li jidhru differenzi kbar bejn individwu u ieħor fil- farmakokinetika ta ’ interferon, huwa irrikkmandat li pazjenti li jkollhom indeboliment renali sever ikunu monitorjati mill- qrib waqt kura bi PegIntron (ara sezzjoni 4. 2).
Hepatic function:
Funzjoni tal- fwied:
The pharmacokinetics of PegIntron have not been evaluated in patients with severe hepatic dysfunction.
Il- farmakokinetika ta ’ PegIntron ma ġietx studjata f’ pazjenti li għandom funzjoni ħażina severa tal- fwied.
Elderly patients ≥ 65 years of age:
Pazjenti anzjani ≥ 65 sena:
The pharmacokinetics of PegIntron following a single subcutaneous dose of 1.0 microgram/kg were not affected by age.
Il- farmakokinetiċi ta ’ PegIntron wara doża waħda ta ’ 1. 0 mikrogramma/ kg mogħtija taħt il- ġilda ma kenitx affetwata bl- età.
The data suggest that no alteration in PegIntron dosage is necessary based on advancing age.
L- informazzjoni tissuġġerixxi li ma hemm bżonn ta ’ ebda tibdil fid- doża ta ’ PegIntron f’ età avvanzata.
Patients under the age of 18 years:
Pazjenti taħt 18- il sena:
Specific pharmacokinetic evaluations have not been performed on these patients.
Evwalazzjonijiet farmakokinetiċi speċifiċi ma twettqux fuq dawn il- pazjenti.
PegIntron is indicated for the treatment of chronic hepatitis C only in patients 18 years of age or older.
PegIntron huwa intiż biss għat- trattament ta ’ epatite Ċ kronika f’ pazjenti li għandhom 18- il sena jew aktar.
Interferon neutralising factors:
Fatturi li jinnewtralizzaw l- interferon:
Interferon neutralising factor assays were performed on serum samples of patients who received PegIntron in the clinical trial.
Assays tal- fatturi li jinnewtralizzaw l- interferon saru fuq kampjuni ta ’ serum ta ’ pazjenti li ngħataw PegIntron fil- prova klinika.
Interferon neutralising factors are antibodies which neutralise the antiviral activity of interferon.
Il- fatturi li jinnewtralizzaw interferon huma antikorpi li jinnewtralizzaw l- attività ta ’ l- interferon kontra l- vajrus.
The clinical incidence of neutralising factors in patients who received PegIntron 0.5 micrograms/kg is 1.1%.
L- inċidenza klinika tal- fatturi newtralizzanti f’ pazjenti li ngħataw PegIntron 0. 5 mikrogramma/ kg hija ta ’ 1. 1%.
Adverse events not observed in clinical trials were not seen in toxicity studies in monkeys.
Effetti avversi li ma dehrux fl- istudji kliniċi lanqas ma dehru fi studji dwar tossiċità li saru fuq xadini.
These studies were limited to four weeks due to the appearance of anti-interferon antibodies in most monkeys.
Dawn l- istudji kienu limitati għal tul ta ’ erba ’ ġimgħat minħabba li tfaċċaw antikorpi kontra l - interferon fil- biċċa l- kbira tax- xadini.
Reproduction studies of PegIntron have not been performed.
Studji ta ’ l- effett ta ’ PegIntron fuq ir- riproduzzjoni għadhom ma twettqux.
PegIntron is likely to also cause this effect.
Intwera illi interferon alfa- 2b jikkawża l- abort fix- xadini u x’ aktarx illi PegIntron ukoll għandu dan l- effett.
Effects on fertility have not been determined.
Effetti fuq il- fertilità għadhom ma ġewx stabbiliti.
It is not known whether the components of this medicinal product are excreted into experimental animal or human milk (see section 4.6 for relevant human data on pregnancy and lactation).
M’ huwiex magħruf jekk il- komponenti ta ’ dan il- prodott mediċinali jiġux eliminati ġol - ħalib tal- bniedem jew ta ’ l- annimali li jintużaw fl- esperimenti (ara sezzjoni 4. 6 għal dejta rilevanti fuq il - bniedem waqt it- tqala u treddigħ).
PegIntron showed no genotoxic potential.
PegIntron ma deherx li seta ’ jagħmel ħsara ġenotossika.
The relative non-toxicity of monomethoxy-polyethylene glycol (mPEG), which is liberated from PegIntron by metabolism in vivo has been demonstrated in preclinical acute and subchronic toxicity studies in rodents and monkeys, standard embryo-foetal development studies and in in vitro mutagenicity assays.
Meta mqabbel mal- monomethoxy- polyethylene glycol tal- monomethoxy- polyethylene glycol (mPEG), illi jinħeles minn ma 'PegIntron waqt il- metaboliżmu in vivo in- nuqqas ta ’ tossiċità relattiva ġiet stabbilita fi studji li saru qabel l- użu kliniku fuq tossiċità akuta u sotto- kronika illi saru fuq firien u xadini, studji standard fuq l- iżvilupp embrijo- fetali u assays in vitro fuq mutaġeniċità.
PegIntron plus ribavirin:
PegIntron flimkien ma 'ribavirin:
When used in combination with ribavirin, PegIntron did not cause any effects not previously seen with either active substance alone.
Meta ġie wżat flimkien ma ’ ribavirin, PegIntron ma kkawża l- ebda effett li ma kienx digà deher b’ wieħed mis- sustanzi attivi waħidhom.
The major treatment-related change was a reversible, mild to moderate anaemia, the severity of which was greater than that produced by either active substance alone.
L- akbar bidla relatata mat- trattament kienet anemija ħafifa għal moderata riversibbli, u li s- serjetà tagħha kienet akbar minn dik ikkaġunata minn xi waħda mis- sustanzi attivi waħidhom.
Powder for solution for injection:
Trab li jinħall f’ soluzzjoni għall- injezzjoni:
Disodium phosphate, anhydrous, Sodium dihydrogen phosphate dihydrate, Sucrose, Polysorbate 80.
Disodium phosphate, anhydrous, Sodium dihydrogen phosphate dihydrate, Sukrożju, Polysorbate 80.
Solvent for parenteral use:
Solvent għall- użu parenterali:
22 Water for injections.
Ilma għall- injezzjoni
This medicinal product should only be reconstituted with the solvent provided (see section 6.6).
Dan il- prodott mediċinali għandu jkun rikostitwit biss bis- solvent provdut (ara wkoll sezzjoni 6. 6).
- Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8ºC.
- Stabbilità kimika u fiżika ta ’ waqt l- użu ġiet stabbilita għal 24 siegħa f’ temperatura ta ’ bejn 2°C - 8ºC
- From a microbiological point of view, the product is to be used immediately.
- Mil- lat mikrobijoloġiku, il- prodott għandu jintuża mill- ewwel.
If not used
Jekk mhux użat mill- ewwel, iż- żmien
immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C.
kemm idum merfugħ waqt l- użu u l- kundizzjonijiet qabel ma jintuża huma r- responsabbiltà ta ’ min qed juża l- mediċina u s- soltu m’ għandux ikun itwal minn 24 siegħa f’ temperatura ta ’ bejn 2°C - 8°C.
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.
The solvent is presented in a 2 ml ampoule, Type I flint glass.
Is- solvent jiġi f’ ampulla ta ’ 2 ml, bi ħġieġ taż- żnied tat- Tip I.
PegIntron 50 micrograms is supplied as:
PegIntron 50 mikrogrammi jiġi bħala:
- 1 vial of powder for solution for injection and 1 ampoule of solvent for parenteral use;
- 1 kunjett ta ’ trab għal soluzzjoni għall- injezzjoni u 1 ampulla ta ’ solvent għall- użu parenterali;
- 1 vial of powder for solution for injection, 1 ampoule of solvent for parenteral use, 1 injection
- 1 kunjett ta ’ trab għal soluzzjoni għall- injezzjoni, u 1 ampulla ta ’ solvent għall- użu parenterali, 1 siringa
syringe, 2 injection needles and 1 cleansing swab;
għall- injezzjoni, 2 labriet ta ’ l- injezzjoni u 1 biċċa għat- tindif;
- 4 vials of powder for solution for injection and 4 ampoules of solvent for parenteral use;
- 4 kunjetti ta ’ trab għal soluzzjoni għall- injezzjoni u 4 ampulli ta ’ solvent għall- użu parenterali;
- 4 vials of powder for solution for injection, 4 ampoules of solvent for parenteral use, 4 injection
- 4 kunjetti ta ’ trab għal soluzzjoni għall- injezzjoni, 4 ampulli ta ’ solvent għall- użu parenterali, 4 siringi
syringes, 8 injection needles and 4 cleansing swabs;
għall- injezzjoni, 8 labriet ta ’ l- injezzjoni u 4 biċċa għat- tindif;
- 6 vials of powder for solution for injection and 6 ampoules of solvent for parenteral use.
- 6 kunjetti ta ’ trab għal soluzzjoni għall- injezzjoni u 6 ampulli ta ’ solvent għall- użu parenterali.
- 12 vials of powder for solution for injection, 12 ampoules of solvent for parenteral use, 12 injection
- 12- il kunjett ta ’ trab għal soluzzjoni għall- injezzjoni, 12- il ampulla ta ’ solvent għall- użu parenterali, 12 -
syringes, 24 injection needles and 12 cleansing swabs.
il siringa għall- injezzjoni, 24 labra ta ’ l- injezzjoni u 12- il biċċa għat- tindif;
Not all pack sizes may be marketed
Jista’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
PegIntron is supplied as a powder of peginterferon alfa-2b at a strength of 50 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 ’ 50 mikrogrammi li jista ’ jintuża darba biss.
Each vial must be reconstituted with 0.7 ml of water for injections for administration of up to 0.5 ml of solution.
Kull kunjett għandu jkun rikostitwita b '0. 7 ml ta ’ ilma għall- injezzjonijiet biex tingħata sa 0. 5 ml ta ’ soluzzjoni.
A small volume is lost during preparation of PegIntron for injection when the dose is measured and injected.
Volum żgħir jintilef waqt il- preparazzjoni ta ’ PegIntron għall- injezzjoni meta d- doża tiġi mkejla u injettata.
Therefore, each vial 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 kunjett 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/0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 50 mikrogrammi/ 0. 5 ml.
Using a sterilised injection syringe and injection needle, inject 0.7 ml of water for injections into the vial of PegIntron.
Permezz ta ’ siringa sterilizzata għall- injezzjoni u labra ta ’ l- injezzjoni, injetta 0. 7 ml ta ’ ilma għall - injezzjonijiet ġol- kunjett ta ’ PegIntron.
Agitate gently to complete dissolution of powder.
Ħawwad bil- mod sabiex jinħall it- trab.
The appropriate dose can then be withdrawn with a sterilised injection syringe and injected.
Id- doża xierqa tista ’ mbagħad tinġibed permezz ta ’ siringa għall- injezzjoni sterilizzata u tiġi injettata.
A complete set of instructions is provided in the Annex to the Package Leaflet.
Sett ta ’ istruzzjonijiet komplet jiġi ma ’ l- Anness tal- Fuljett ta ’ Tagħrif.
As for all parenteral medicinal products, inspect visually the reconstituted solution prior to administration.
Bħall- prodotti mediċinali kollha għall- użu parenterali, ifli s- soluzzjoni rikostitwita qabel ma tagħtiha.
The reconstituted solution should be clear and colourless.
Is - soluzzjoni rikostitwita għandha tkun ċara u bla kulur.
Do not use if discolouration or particulate matter is present.
Tużax jekk ikun hemm bidla fil- kulur jew xi frak.
Discard any unused material.
Armi kull materjal li ma jkunx intuża.
MARKETING AUTHORISATION HOLDER
ID- DETENTUR TA ’ L- AWTORIZZAZZJONI GĦ AT- TQEGĦ ID FIS- SUQ
MARKETING AUTHORISATION NUMBERS
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦ ID FIS- SUQ
Date of first authorisation:
Data ta’ l- ewwel awtorizzazzjoni:
25 May 2000 Date of last renewal:
25 ta ’ Mejju 2000 Data ta ’ l- aħħar tiġdid:
25 May 2005
25 ta ’ Mejju 2005
Detailed information on this product is available on the web-site of the European Medicines Agency (EMEA) http://www.emea.europa.eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
PegIntron 80 micrograms powder and solvent for solution for injection
PegIntron 80 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial of PegIntron, powder for solution for injection contains 80 micrograms of peginterferon alfa-2b as measured on a protein basis.
Kull kunjett ta ’ PegIntron, trab għal soluzzjoni għall- injezzjoni fih 80 mikrogrammi ta ’ peginterferon alfa- 2b hekk kif imkejjel fuq bażi ta ’ proteina.
Each vial provides 80 micrograms/0.5 ml of peginterferon alfa-2b when reconstituted as recommended.
Kull kunjett jipprovdi 80 mikrogrammi/ 0. 5 ml ta ’ peginterferon alfa- 2b meta rikostitwit kif rakkomandat.
For more inform ation, see section 5.1. *produced by rDNA technology in E.coli cells harbouring a genetically engineered plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes
Għal aktar informazzjoni, ara sezzjoni 5. 1. * magħmul bit- teknoloġija ta ’ rDNA f’ ċelluli E. coli bl- istess plasmid ibrida li jkun fiha ġene ta ’ interferon alfa- 2b minn ċelluli ta ’ lewkoċiti umani.
25 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.
The intended dose of 1.5 μg/kg of PegIntron to be used in combination with ribavirin may be delivered in weight categories with the pen/vial strengths according to Table 1.
Id- doża maħsuba ta ’ 1. 5 μg/ kg ta ’ PegIntron li għandha tintuża flimkien ma 'ribavirin tista ’ tingħata f’ kategoriji ta ’ piż bil- qawwiet tal- pinna/ kunjett skond Tabella 1.
Vial/Pen Strength
Doża Totali ta ’
(μg/0.5ml)
Kuljum (mg)
For patients who exhibit virological response at week 12, treatment should be continued for another nine month period (i.e., a total of 48 weeks).
Għal pazjenti li juru reazzjoni viroloġika fil- ġimgħa 12, it- trattament għandu jitkompla għal perijodu ieħor ta ’ disa ’ xhur (i. e., total ta ’ 48 ġimgħa).
In the subset of patients with genotype 1 infection and low viral load (< 600,000 IU/ml) who become HCV-RNA negative at treatment week 4 and remain HCV-RNA negative at week 24, the treatment could either be stopped after this 24 week treatment course or pursued for an additional 24 weeks (i.e. overall 48 weeks treatment duration).
Fis- sottogrupp ta ’ pazjenti b’ infezzjoni tal- ġenotip 1 u viral load baxx (< 6000, 000 IU/ ml) li jsiru negattivi għal HCV- RNA mar- 4 ġimgħa ta ’ kura u jibqgħu negattivi għal HCV- RNA ma ’ l - 24 ġimgħa ta ’ kura, il- kura tista ’ titwaqqaf wara dan il- kors ta ’ 24 ġimgħa jew jitkompla għal 24 ġimgħa oħra (i. e. b’ kollox 48 ġimgħa ta ’ kura).
It is recommended that all patients be treated for 24 weeks, except for HCV/HIV co-infected patients who should receive 48 weeks of treatment. • Genotype 4:
Huwa rakkomandat illi l- pazjenti jiġu ttrattati għal mill- inqas 24 ġimgħa, ħlief għall- pazjenti li jkollhom infezzjoni fl- istess ħin b’ HCV/ HIV li għandhom jirċievu kura ta ’ 48 ġimgħa. • Ġenotip 4:
HCV/HIV Co-infection The recommended duration of dosing for HCV/HIV co-infected patients is 48 weeks, regardless of genotype.
Infezzjoni fl- istess ħin b’ HCV/ HIV It- tul tad- dużaġġ rakkomandat għall- pazjenti li jkollhom infezzjoni fl- istess ħin b’ HCV/ HIV huwa ta ’ 48 ġimgħa, ikun x’ ikun il- ġenotip.
Early virological response by Week 12, defined as a 2 log viral load decrease or undetectable levels of HCV-RNA, has been shown to be predictive for sustained response.
Kemm jista ’ jkun imbassar ir- rispons jew in- nuqqas tiegħu f ’ infezzjonijiet fl- istess ħin b’ HCV/ HIV Rispons viroloġiku bikri ma ’ Ġimgħa 12, definit bħala 2 log tal- viral load jew livelli li ma jitkejlux ta ’ HCV- RNA, deher li setgħa jservi għat- tbassir ta ’ rispons sostnut.
The negative predictive value for sustained response in HCV/HIV co-infected patients treated with PegIntron in combination with ribavirin was 99% (67/68; Study 1) (see section 5.1).
Il- valur ta ’ tbassir negattiv għal rispons sostnut f’ pazjenti infettati fl- istess ħin b’ HCV/ HIV ikkurati b’ PegIntron f’ kombinazzjoni ma ’ ribavirin kien 99% (67/ 68; Studju 1) (ara sezzjoni 5. 1).
A positive predictive value of 50% (52/104; Study 1) was observed for HCV/HIV co-infected patients receiving combination therapy.
Valur ta ’ tbassir pożittiv ta ’ 50% (52/ 104; Studju 1) deher għal pazjenti infettati fl- istess ħin b’ HCV/ HIV li kienu qed jirċievu terapija kombinata.
26 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/kg/week.
Monoterapija b’ PegIntron Bħala monoterapija l- kors ta ’ PegIntron huwa ta ’ 0. 5 jew 1. 0 mikrogramma/ kg/ ġimgħa.
The lowest vial or pen strength available is 50 μg/0.5 ml; therefore for patients prescribed 0.5 μg/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.
For the 1.0 μg/kg dose, similar volume adjustments can be made or alternate vial strengths can be used as shown in Table 2.
Għad - doża ta ’ 1. 0 μg/ kg, aġġustamenti fil- volum bħal dawn jistgħu jsiru jew inkella jistgħu jintużaw kunjetti b’ qawwiet oħra kif muri f’ Tabella 2.
PegIntron monotherapy was not studied in HCV/HIV co-infected patients.
Monoterapija b’ PegIntron ma kienitx studjata f’ pazjenti ko- infettati b’ HCV/ HIV.
Vial/Pen Strength
Qawwa tal -
Administer Vial/Pen Once Weekly Strength
Amministra Qawwa tal -
Administer Once Weekly
Pinna/ Kunjett (μg/ 0. 5ml)
(μg/0.5 ml)
Darba fil - Pinna/ Kunjett Ġimgħa (μg/ 0. 5ml) (ml)
(ml) (μg/0.5ml)
Darba fil - Ġimgħa (ml)
(ml)
50 * 50 * 50 * 50 50
30-35 36-45 46-56 57-72 73-88 89-106 > 106**
89- 106 > 106 **
Minimum delivery for pen is 0.3 ml. ** For patients > 120 kg, use 80 μg/0.5 ml vial
L- inqas ammont mogħti mill- pinna huwa ta ’ 0. 3 ml. ** Għal pazjenti > 120 kg, uża kunjett ta ’ 80 μg/ 0. 5 ml
Duration of treatment For patients who exhibit virological response at Week 12, treatment should be continued for at least another three-month period (i.e., a total of six months).
Tul tat- trattament Għal pazjenti li juru reazzjoni viroloġika f’ Ġimgħa 12, it- trattament għandu jitkompla għal perijodu ieħor ta ’ mill- inqas tliet xhur (i. e., total ta ’ sitt xhur).
The decision to extend therapy to one year of treatment should be based on prognostic factors (e.g., genotype, age > 40 years, male gender, bridging fibrosis).
Id- deċiżjoni biex it- terapija tkun estiża għal sena ta ’ trattament għandha tkun ibbażata fuq fatturi pronostiċi (eż., ġenotip, età > 40 sena, sess maskil, fibrożi li tgħaqad).
27 Combination Therapy Dose Reduction Guidelines
Linji Gwida Dwar it- Tnaqqis fid- Doża tat- Terapija Kombinata
ribavirin dose to 600 mg/day* if:
600 mg/ kuljum * biss jekk:
< 8.5 g/dl
< 8. 5 g/ dl
g/dl decrease in haemoglobin during any four week period during treatment (permanent dose reduction) - < 1.5 x 109/l - < 0.75 x 109/l 9
erba ’ ġimgħat waqt it- trattament (tnaqqis permanenti fid- doża)
12 g/dl after four weeks of dose reduction < 1.0 x 109/l < 0.5 x 109/l
< 0. 5 x 109/ l < 25 x 109/ l
- < 50 x 10 /l - - > 5 mg/dl -
> 5 mg/ dl -
< 25 x 109/l 2.5 x ULN ** > 4 mg/dl (for > 4 weeks)
> 4 mg/ dl > 4 ġimgħat)
> 2.0 mg/dl 2 x baseline and > 10 x ULN**
2 x linja bażi u > 10 x ULN **
Vial/Pen
Saħħa tal -
Dose (μg)
fid- Doża (μg)
(μg/0.5 ml)
Kunjett/ Pinna (μg/ 0. 5 ml)
0. 25
0. 25
< 0.75 x 109/l
< 0. 75 x 109/ l
< 0.5 x 109/l
< 0. 5 x 109/ l
28 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.
The 50 μg/0.5 ml vial must be used if necessary since the pen can only deliver a minimum volume of 0.3 ml.
Il- kunjett ta ’ 50 μg/ 0. 5 ml għandha tintuża jekk meħtieġ billi l- pinna tista ’ biss twassal volum minimu ta ’ 0. 3 ml.
For patients who use 1.0 μg/kg PegIntron monotherapy, dose reduction may be accomplished by reducing the prescribed volume by one-half or by utilizing a lower dose strength as shown in Table 3b.
Għal pazjenti illi jużaw il- monoterapija ta ’ PegIntron 1. 0 μg/ kg, tnaqqis fid- doża jista ’ jinkiseb billi jitnaqqas il- volum li ġie miktub mit- tabib bin- nofs jew billi tintuża doża anqas qawwija kif muri f 'Tabella 3b.
Table 3b – Reduced PegIntron Dose for the 1.0 μg/kg Monotherapy Regimen
Tabella 3b – Tnaqqis fid- Doża ta ’ PegIntron għall- Kors ta ’ Monoterapija 1. 0 μg/ kg
Dose (μg)
Doża
(μg/0.5 ml)
Intenzjonat (μg)
0. 15
0. 15
0. 20
0. 20
Peg Intron should be used with caution in patients with moderate to severe renal impairment.
Monoterapija: PegIntron għandu jintuża b’ attenzjoni f’ pazjenti b’ indeboliment renali moderat għal sever.
In patients with moderate renal dysfunction (creatinine clearance 30- 50 ml/minute), the starting dose of PegIntron should be reduced by 25%.
F’ pazjenti li jkollhom il- funzjoni renali ħażina b’ mod moderat (tneħħija tal- krejatinina 30- 50 ml/ minuta), id- doża tal- bidu ta ’ PegIntron għandha titnaqqas b’ 25%.
Patients with severe renal dysfunction (creatinine clearance 15-29 ml/minute) should have the starting dose of PegIntron reduced by 50%.
Pazjenti li jkollhom funzjoni renali ħażina b’ mod sever (tneħħija tal- krejatinina 15- 29 ml/ min) għandhom jieħdu d- doża tal- bidu ta ’ PegIntron imnaqqsa b’ 50%.
Data are not available for the use of PegIntron in patients with creatinine clearance < 15 ml/minute (see section 5.2).
M’ hemmx tagħrif dwar l- użu ta ’ PegIntron f’ pazjenti bi tneħħija tal - krejatinina < 15 ml/ min (ara sezzjoni 5. 2).
Patients with creatinine clearance < 50 ml/minute must not be treated with PegIntron in combination with ribavirin (see ribavirin SPC).
Terapija kombinata: Pazjenti bit- tneħħija tal- krejatinina < 50 ml/ minuta m’ għandhom jiġu kkurati b’ PegIntron f’ taħlita ma ’ ribavirin (ara SPC ta ’ ribavirin).
- A history of severe pre-exist ing cardiac disease, including unstable or uncontrolled cardiac disease
- Passat ta ’ mard tal- qalb sever pri- eżistenti, inkluż mard tal- qalb mhux stabbli jew mhux kontrollat fis -
- Epilepsy and/or compromised central nervous system (CNS) function;
- Epilessija u/ jew funzjoni kompromessa tas- sistema nervuża ċentrali (CNS);
- Initiation of PegIntron is contraindicated in HCV/HIV patients with cirrhosis and a Child-Pugh
- Huwa kontra- indikat li tinbeda kura bi PegIntron f’ pazjenti HCV/ HIV b’ ċirrożi u punteġġ Child- Pugh
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i.e. patients with genotype 2 and 3), treatment may be possible without histological confirmation.
Il- pazjenti kollha fl- istudji li saru dwar epatite Ċ kronika saritilhom bijopsija tal- fwied qabel ma ġew inklużi, iżda f’ ċertu każijiet (jiġifieri pazjenti b’ ġenotip 2 u 3), it- trattament jista ’ jkun possibbli mingħajr konferma istoloġika.
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) have been observed rarely during interferon alfa-2b therapy.
Reazzjonijiet rari ta ’ sensittività eċċessiva akuta (eż urtikarja, anġjo- edema, bronko- kostrizzjoni, anafilassi) ġew osservati rarament waqt it- terapija ta ’ interferon alfa- 2b.
As with interferon alfa-2b, patients with a history of congestive heart failure, myocardial infarction and/or previous or current arrhythmic disorders, receiving PegIntron therapy require close monitoring.
Bħalma jiġri b 'interferon alfa- 2b, pazjenti li għandhom passat ta ’ insuffiċjenza tal - qalb konġestiva, attakk tal- qalb kif ukoll/ jew li kellhom jew għandhom problemi arritmiċi u li qed jingħataw terapija b’ PegIntron jeħtieġu sorveljanza mill- qrib.
30 Hydration:
Idratazzjoni:
HCV/HIV Co-infection Mitochondrial toxicity and lactic acidosis:
Infezzjoni fl- istess ħin b’ HCV/ HIV Tossiċità mitokondrijali u aċidożi lattika:
Hepatic decompensation in HCV/HIV co-infected patients with advanced cirrhosis:
Pazjenti infettati fl- istess ħin HCV/ HIV li jkollhom ċirrożi fi stat avvanzat:
31 Haematological abnormalities in HCV/ HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
HCV/HIV co-infected patients receiving peginterferon alfa-2b/ribavirin treatment and HAART may be at increased risk to develop haematological abnormalities (as neutropenia, thrombocytopenia and anaemia) compared to HCV mono-infected patients.
F’ pazjenti li jkollhom fl- istess ħin HCV/ HIV li jkunu qed jirċievu kura bi peginterferon alfa- 2b/ ribavirin u HAART jista ’ jkollhom riskju akbar li jiżviluppaw anormalitajiet ematoloġiċi (bħal newtropenja, tromboċitopenja u anemija) meta mqabbla ma ’ pazjenti infettati b’ HCV waħdu.
Although, the majority of them could be managed by dose reduction, close monitoring of haematological parameters should be undertaken in this population of patients (see section 4.2 and below “Laboratory tests” and section 4.8).
Għalkemm il- parti l- kbira tagħhom jistgħu jkunu mmaniġġjati bi tnaqqis fid- doża, monitoraġġ mill- qrib ta ’ parametri ematoloġiċi għandu jsir f’ din il- popolazzjoni ta ’ pazjenti (ara sezzjonijiet 4. 2 u hawn taħt “ Testijiet tal- Laboratorju ” u sezzjoni 4. 8).
In patients co-infected with HCV/HIV, limited efficacy and safety data (N = 25) are available in subjects with CD4 counts less than 200 cells/µl.
F’ pazjenti li jkollhom fl- istess ħin HCV/ HIV, dejta dwar l- effikaċja u s- sigurtà limitata (N=25) huma disponibbli f’ individwi b’ għadd tas- CD4 anqas minn 200 cellula/ µl.
Dental and periodontal disorders, which may lead to loss of teeth, have been reported in patients receiving Peg Intron and ribavirin combination therapy.
Disturbi tas- snien u tal- ħanek: Disturbi tas- snien u tal- ħanek, li jistgħu jwasslu għal telf ta ’ snien, kienu rrappurtati f’ pazjenti li kienu qed jirċievu PegIntron u ribavirin f’ terapija kombinata.
Caution should be used when admin istering peginterferon alfa-2b with medicinesmetabolised by CYP2D6 and CYP2C8/9, especially those with narrow therapeutic window, such as warfarin and phenytoin (CYP2C9) and flecainide (CYP2D6).
Għandha ssir attenzjoni meta jingħata peginterferon alfa- 2b ma ’ mediċini metabolizzati b’ CYP2D6 u CYP2C8/ 9, l- aktar dawk b’ firxa terapewtika dejqa, bħal warfarin u phenytoin (CYP2C9) u flecainide (CYP2D6).
No pharmacokinetic interactions were noted between Peg Intron and ribavirin in a multiple-dose pharmacokinetic study.
Ma kienx hemm interazzjonijiet farmakokinetiċi sinifikanti bejn PegIntron u ribavirin fi studju farmakokinetiku fejn ingħataw ħafnadożi.
There are no adequate data from the use of interferon alfa-2b in pregnant women..
M’ hemmx tagħrif xieraq dwar l- użu ta ’ interferon alfa- 2b f’ nisa waqt it- tqala.
PegIntron is to be used during pregnancy only if the potential benefit justifies the potential risk to the foetus
PegIntron għandu jintuża waqt it- tqala biss jekk il- benefiċċju li jista ’ jkun hemm jiġġustifika r- riskju li jista ’ jkun hemm għall- fetu.
33 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.
Infections and infestations Very common:
Infezzjonijiet u infestazzjonijiet Komuni ħafna:
34 Metabolism and nutrition disorders Very common:
Dijabete Disturbi fil- metaboliżmu u n - nutrizzjoni Komuni ħafna:
Interstitial lung disease 35
Disturbi gastro- intestinali Komuni ħafna:
36 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).
Haematological abnormalities were more frequently reported in patients receiving PegIntron in combination with ribavirin when compared to patients receiving interferon alfa-2b in combination with ribavirin.
Anormalitajiet ħematoloġiċi kienu rrappurtati b’ mod aktar frekwenti f’ pazjenti li kienu qed jirċievu PegIntron f’ kombinazzjoni ma ’ ribavirin meta mqabbel ma ’ pazjenti li kienu qed jirċievu interferon alfa- 2b flimkien ma ’ ribavirin.
37 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 clinical trials – Naïve patients Two pivotal trials have been conducted, one (C/I97-010) with PegIntron mono therapy; 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.
38 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).
However, response rates in this trial were shown to be dependent also on the dose of ribavirin administered in combination with PegIntron or interferon alfa-2b.
Madankollu intwera li r- rati ta ’ reazzjoni f’ dan l- istudju kienu jiddependu wkoll fuq id - doża ta ’ ribavirin li ngħatat flimkien ma 'PegIntron jew interferon alfa- 2b.
P 1.5 Peg Intron 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 * **
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) p < 0.001 P 1.5 vs.
PegIntron (1. 5 mikrogrammi/ kg) + ribavirin (800 mg) PegIntron (1. 5 sa 0. 5 mikrogramma/ kg) + ribavirin (1, 000/ 1, 200 mg) Interferon alfa- 2b (3 MIU) + ribavirin (1, 000/ 1, 200 mg) p < 0. 001 P 1. 5 vs.
39 Genotype 2/3
Ġenotip 2/ 3
All
Kollha ≤ 10. 6 > 10. 6
Peg Intron (1.5 microgr ams/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)
In the PegIntron monotherapy study, the Quality of Life was generally less affected by 0.5 microgram/kg of PegIntron than by either 1.0 microgram/kg of PegIntron once weekly or 3 MIU of interferon alfa-2b three times a week.
Fl- istudju fejn ingħatat monoterapija b 'PegIntron, il- Kwalità tal- Ħajja kienet ġeneralment inqas affettwata b’ 0. 5 mikrogramma/ kg ta ’ PegIntron milli jew b’ 1. 0 mikrogramma/ kg ta ’ PegIntron darba fil- ġimgħa jew b’ 3 MIU ta ’ interferon alfa- 2b tliet darbiet fil- ġimgħa.
* Any subject with an undetectable HCV-RNA level at the Follow-Up Week 12 visit and missing data at the Follow- Up Week 24 visit was considered a sustained responder.
Żjara ma ’ Ġimgħa 24 kienet meqjusa bħala rispons sostnut.
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 *
Treatment PegIntron 1.5 + ribavirin (> 10.6 mg/kg) 48-week treatment PegIntron 1.5 + ribavirin 800-1,400 mg
Kura PegIntron 1. 5 + ribavirin (> 10. 6 mg/ kg)
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%
No 1% (2/215) 50% (1/2) 50%
Le 1% (2/ 215)
with 12 week data available
* jirrifletti pazjenti li għandhom dejta ta ’ 12- il gimgħa
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 41 2 previously untreated adult patients with chronic hepatitis C who were co-infected with HIV.
Studju 1 (RIBAVIC; P01017) kien studju multiċentriku randomized li fih ħadu sehem 412 pazjent adult li ma kienux ikkurati qabel b’ epatite C kronika li kellhom ukoll infezzjoni b’ HIV.
The duration of therapy 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 6month 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.
41 Table 9
Tabella 9
Sustained virological res ponse 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)
2 Laguno M, Murillas J, Blanco J.L et al.
2 Laguno M, Murillas J, Blanco J. et al.
Both the Metavir score and Ishak grade decreased among subjects treated with Peg Intron in combination with ribavirin.
Kemm il- punteġġ Metavir u l- grad Ishak naqsu fost l- individwi ikkurati b’ PegIntron f’ kombinazzjoni ma ’ ribavirin.
42 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)
60.0 (9/ 15) 27.4, 92.6
60. 0 (9/ 15) 27. 4, 92. 6
46.0 (63/137) 35.0, 57.0
46. 0 (63/ 137) 35. 0, 57. 0
Plasma HCV-RNA is measured with a research-based quantitative polymerase chain reaction assay by a central laboratory * Intent to treat population includes 7 patients for whom at least 12 weeks of prior therapy could not be confirmed.
HCV- RNA fil- plażma jitkejjel b’ essej ta ’ reazzjoni ta ’ katina tal- polymeras kwantitattiv ibbażat fuq riċerka minn laboratorju ċentrali. * Popolazzjoni bl- intenzjoni li tiġi ikkurata tinkludi 7 pazjenti li għalihom mill- anqas 12- il ġimgħa ta ’ terapija minn qabel ma setgħetx tkun ikkonfermata.
43 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).
Renal clearance appears to account for 30% of total clearance of PegIntron.
Jidher illi l- clearance mill- kliewi hija responsabbli għal 30% tar- rata kollha ta ’ eliminazzjoni ta ’ PegIntron.
44 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).
45 Water for injections.
Ilma għall- injezzjoni
PegIntron 80 micrograms is supplied as:
PegIntron 80 mikrogrammi jiġi bħala:
PegIntron is supplied as a powder of peginterferon alfa-2b at a strength of 80 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 ’ 80 mikrogrammi li jista ’ jintuża darba biss.
The reconstituted solution has a concentration of 80 micrograms/0.5 ml.
Is- soluzzjoni rikostitwita għandha konċentrazzjoni ta ’ 80 mikrogrammi/ 0. 5 ml.
PegIntron 100 micrograms powder and solvent for solution for injection
PegIntron 100 mikrogrammi trab u solvent għal soluzzjoni għall- injezzjoni.
Each vial of PegIntron, powder for solution for injection contains 100 micrograms of peginterferon alfa- 2b as measured on a protein basis.
Kull kunjett ta ’ PegIntron, trab għal soluzzjoni għall- injezzjoni fih 100 mikrogrammi ta ’ peginterferon alfa - 2b hekk kif imkejjel fuq bażi ta ’ proteina.
Each vial provides 100 micrograms/0.5 ml of peginterferon alfa-2b when reconstituted as recommended.
Kull kunjett jipprovdi 100 mikrogrammi/ 0. 5 ml ta ’ peginterferon alfa- 2b meta rikostitwit kif rakkomandat.
For more information, see section 5.1. *produced by rDNA technology in E.coli cells harbouring a genetically engineered plasmid hybrid encompassing an interferon alfa-2b gene from human leukocytes
Għal aktar informazzjoni, ara sezzjoni 5. 1. * magħmul bit- teknoloġija ta ’ rDNA f’ ċelluli E. coli bl- istess plasmid ibrida li jkun fiha ġene ta ’ interferon alfa- 2b minn ċelluli ta ’ lewkoċiti umani.
PegIntron is indicated for the treatment of adult patients with chronic hepatitis C who have elevated transaminases without liver decompensation and who are positive for serum HCV-RNA or anti-HCV, including naïve patients with clinically stable HIV co-infection (see section 4.4).
PegIntron jintuża għat- trattament ta ’ pazjenti adulti b’ epatite Ċ kronika li għandhom transaminases għoljin mingħajr nuqqas ta ’ kumpensament tal- fwied u li huma pożittivi għal HCV- RNA fis- serum jew anti- HCV inklużi pazjenti naïve b’ ko- infezzjoni ta ’ HIV klinikament stabbli (ara sezzjoni 4. 4).
48 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.
Early virological response by Week 12, defined as a 2 log viral load decrease or undetectable levels of HCV-RN A, has been shown to be predictive for sustained response.
Kemm jista ’ jkun imbassar ir- rispons jew in- nuqqas tiegħu f ’ infezzjonijiet fl- istess ħin b’ HCV/ HIV Rispons viroloġiku bikri ma ’ Ġimgħa 12, definit bħala 2 log tal- viral load jew livelli li ma jitkejlux ta ’ HCV- RNA, deher li setgħa jservi għat- tbassir ta ’ rispons sostnut.