qanastek/EMEA-V3 huggingface dataset:
Genotype 1
Ġenotip 1
 2 million copies/ml Genotype 1
 2 miljun kopja/ ml Ġenotip 1
> 2 million copies/ml
> 2 miljun kopji/ ml
Genotype 2/3
Ġenotip 2/ 3
I IntronA (3 MIU 3 times a week) I/R IntronA (3 MIU 3 times a week) + ribavirin (1,000/1,200 mg/day)
I IntronA (3 MIU 3 darbiet fil- ġimgħa) I/ R IntronA (3 MIU 3 darbiet fil- ġimgħa) + ribavirin (1, 000/ 1, 200 mg/ jum)
HCV/HIV Co-infected patients Two trials have been conducted in patients co-infected with HIV and HCV.
Pazjenti ko - infettati b’ HCV/ HIV Saru żewġ provi f’ pazjenti ko- infettati b’ HIV u HCV.
Overall, in both studies, patients who received IntronA plus ribavirin, were less likely to respond than patients who received pegylated interferon alfa-2b with ribavirin.
B’ mod globali, fiż- żewġ studji, il- pazjenti li rċievew IntronA flimkien ma ’ ribavirin, kellhom anqas ċans li jkollhom rispons minn pazjenti li rċievew interferon alfa- 2b pegilat flimkien ma ’ ribavirin.
The response to treatment in both of these trials is presented in Table 4.
Ir- rispons għall- kura f’ dawn iż- żewġ provi qed jidher f’ Tabella 4.
Study 1 (RIBAVIC; P01017) was a randomized, multicentre study which enrolled 412 previously untreated adult patients with chronic hepatitis C who were co-infected with HIV.
Studju 1 (RIBAVIC; P01017) kien studju randomized, multiċentriku li ingaġġa 412 pazjent adult li ma kienux ingħataw kura minn qabel b’ epatite Ċ kronika li kienu ko- infettati b’ HIV.
Patients were randomized to receive either pegylated interferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800 mg/day) or IntronA (3 MIU TIW) plus ribavirin (800 mg/day) for 48 weeks with a follow-up period of 6 months.
Il- pazjenti kienu randomized biex jirċievu interferon alfa- 2b pegilat (1. 5 µg/ kg/ ġimgħa) flimkien ma ’ ribavirin (800 mg/ jum) jew inkella IntronA (3 MIU TIW) flimkien ma ’ ribavirin (800 mg/ jum) għal 48 ġimgħa b’ perijodu ta ’ follow- up ta ’ 6 xhur.
Study 2 (P02080) was a randomized, single centre study that enrolled 95 previously untreated adult patients with chronic hepatitis C who were co-infected with HIV.
Studju 2 (P02080) kien studju randomised, f’ ċentru wieħed li ingaġġa 95 pazjent adult li ma kienux ingħataw kura minn qabel b’ epatite Ċ kronika li kienu ko- infettati b’ HIV.
Patients were randomized to receive either pegylated interferon alfa-2b (100 or 150 µg /week based on weight) plus ribavirin (800-1,200 mg/day based on weight) or IntronA (3 MIU TIW) plus ribavirin (800-1,200 mg/day based on weight).
Il- pazjenti kienu randomised sabiex jirċievu interferon alfa- 2b pegilat (100 or 150 µg / ġimgħa skond il- piż) flimkien ma ’ ribavirin (800- 1, 200 mg/ jum skond il- piż) jew IntronA (3 MIU TIW) flimkien ma ’ ribavirin (800 mg- 1, 200 mg/ jum skond il- piż).
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 6-month follow-up period.
It - terapija damet 48 ġimgħa b’ perijodu ta ’ follow- up ta ’ 6 xhur ħlief għall- pazjenti li kienu infettati b’ ġenotipi 2 jew 3 u viral load < 800, 000 IU/ ml (Amplicor) li kienu kkurati għal 24 ġimgħa b’ perijodu ta 6 xhur follow- up.
Sustained virological response based on genotype after IntronA in combination with ribavirin versus pegylated interferon alfa-2b in combination with ribavirin in HCV/HIV co-infected patients Study 11 Study 22 pegylated pegylated interferon interferon alfa-2b alfa-2b (100 IntronA (1.5 µg/kg/ IntronA or (3 MIU TIW) week) + (3 MIU TIW) + 150c µg/week) + ribavirin ribavirin ribavirin p + ribavirin (800- p (800 mg) (800 mg) valuea (800- 1,200 mg)d valueb
Rispons viroloġiku sostnut ibbażat fuq il- ġenotip wara IntronA flimkien ma ’ ribavirin kontra interferon alfa- 2b pegilat flimkien ma ’ ribavirin f’ pazjenti ko- infettati b’ HCV/ HIV Studju 11 Studju 22 interferon alfa- 2b pegilat( 100 interferon jew 150c

(3
17 1,200 mg)d
+ ribavirin
All Genotype 1, 4
Kollox Ġenotip 1, 4
27% (56/205) 20% (41/205) 0.047 44% (23/52) 21% (9/43) 17% (21/125) 6% (8/129) 0.006 38% (12/32) 7% (2/27)
44% (23/ 52) 38% (12/ 32)
Genotype 2, 3
Ġenotip 2, 3
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 pegylated interferon alfa-2b and subjects ≥ 75 kg received 150 µg/week pegylated interferon alfa-2b. 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 unit internazzjonali; TIW = tlett darbiet fil- ġmgħa. a: valur p bażat fuq test Cochran- Mantel Haenszel Chi square. b: valur p bażat fuq it- test chi- square. c: individwi < 75 kg irċievew 100 µg/ ġimgħa interferon alfa- 2b pegilat u individwi ≥ 75 kg irċevew 150 µg/ week interferon alfa- 2b pegilat. d: dożi ta ’ ribavirin kien 800 mg għal pazjenti < 60 kg, 1, 000 mg għal pazjenti 60- 75 kg, u 1, 200 mg għal pazjenti > 75 kg.
Relapse patients:
Pazjenti li rkadew:
A total of 345 interferon alpha relapse patients were treated in two clinical trials with IntronA monotherapy or in combination with ribavirin.
Total ta ’ 345 pazjent ta ’ l- interferon alpha li rkadew kienu ittrattati f’ żewġ provi kliniċi bil- monoterapija b’ IntronA jew flimkien ma ’ ribavirin.
In these patients, the addition of ribavirin to IntronA increased by as much as 10-fold the efficacy of IntronA used alone in the treatment of chronic hepatitis C (48.6% vs.
F’ dawn il- pazjenti, meta ribavirin ingħata ma ’ IntronA żied b ’ 10 darbiet l- effettività ta ’ IntronA użat waħdu fit- trattament ta ’ l- epatite Ċ kronika (48. 6% vs.
4.7%).
4. 7%).
This enhancement in efficacy included loss of serum HCV (< 100 copies/ml by PCR), improvement in hepatic inflammation, and normalisation of ALT, and was sustained when measured 6 months after the end of treatment.
Dan it- titjib fl- effettività kien jinkludi t- tnaqqis ta ’ l- HCV fis- serum (< 100 kopja/ ml bil- PCR), it- titjib fl- infjammazzjoni epatika, u n- normalizzazzjoni ta ’ l- ALT, u kien sostnut meta mkejjel 6 xhur wara t- tmiem tat- trattament.
Long-Term efficacy data In a large study, 1,071 patients were enrolled after treatment in a prior non pegylated interferon alfa-2b or non pegylated interferon alfa-2b/ribavirin study to evaluate the durability of sustained virologic response and assess the impact of continued viral negativity on clinical outcomes.
Dejta dwar l- effikaċja fuq Tul ta ’ Żmien Fi studju kbir, 1, 071 pazjent ħadu sehem wara kura fi studju b’ interferon alfa- 2b mhux pegilat jew b’ interferon alfa- 2b mhux pegilat/ ribavirin sabiex jiġi evalwat kemm idum ir- rispons viroloġiku sistnut u jiġi stmat l- impatt ta ’ negattività virali kontinwa fuq il- konsegwenzi kliniċi.
462 patients completed at least 5 years of long-term follow-up and only 12 sustained responders' out of 492 relapsed during this study.
462 pazjent lestew mill- anqas 5 snin tal- follow- up fuq żmien fit- tul u 12 biss minn dawk li wrew rispons minn 492 pazjent irkadew waqt dan l- istudju.
The Kaplan-Meier estimate for continued sustained response over 5 years for all patients is 97% with a 95% Confidence Interval of [95%, 99%].
L- istima Kaplan- Meier għal rispons sostnut fuq 5 snin għall- pazjenti kollha huwa 97% b’ Intervall ta ’ Kunfidenza ta ’ 95% ta ’ [95%, 99%].
SVR after treatment of chronic HCV with non pegylated interferon alfa-2b (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 l- kura ta ’ HCV kronika b’ interferon alfa- 2b mhux pegilat (b’ ribavirin jew mingħajru) irriżulta fi tneħħija fuq żmien fit- tul tal- virus li wasslet għall riżoluzzjoni ta ’ l- infezzjoni epatika u ‘ fejqan ’ kliniku minn HCV kronika.
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 li jkollhom ċirrożi (inkluż tumur epatiku).
Clinical trials in paediatric patients with chronic hepatitis C:
Provi kliniċi f’ pazjenti pedjatriċi b’ epatite Ċ kronika:
Children and adolescents 3 to 16 years of age with compensated chronic hepatitis C and detectable HCV-RNA (assessed by a central laboratory using a research-based RT-PCR assay) were enrolled in two multicentre trials and received IntronA 3 MIU/m2 3 times a week plus ribavirin 15 mg/kg per day for 1 year followed by 6 months follow-up after-treatment.
Tfal u adolexxenti minn 3 sa 16- il sena b’ epatite Ċ kronika kumpensata u HCV- RNA li jista ’ jitkejjel (stmat b’ laboratorju ċentrali b’ assay RT- PCR bażat fuq riċerka) ħadu sehem f’ żewġ provi multiċentriċi u rċevew IntronA 3 MIU/ m2 3 darbiet fil- ġimgħa ma ’ ribavirin 15 mg/ kg għal kul jum għal sena segwit b’ 6 xhur follow- up wara l- kura.
A total of 118 patients were enrolled:
Totali ta ’ 118 pazjent ħadu sehem:
57% male, 80% Caucasian, and 78% genotype 1,64%  12 years of age.
57% irġiel, 80% Kawkażi, u 78% ġenotip 1, 64%  12- il sena.
The population enrolled mainly consisted in children with mild to moderate hepatitis C.
Il- popolazzjoni li ħadet sehem kienet fil- parti l- kbira mgħamula minn tfal b’ epatite Ċ ħafifa għal moderata.
Sustained virological response rates in children and adolescents were similar to those in adults.
Rati ta ’ rispons viroloġiku sostnut fi tfal u adolexxenti kienu simili għal dawk fl- adulti.
Due to the lack of data in children with severe progression of the disease, and the potential for undesirable effects, the benefit/risk of the combination of ribavirin and interferon alfa-2b needs to be carefully considered in this population (see sections 4.1, 4.4 and 4.8).
Minħabba nuqqas ta ’ dejta fi tfal b’ avvanz sever tal - marda, u l- potenzjal ta ’ effetti sekondarji, il- benefiċċju/ riskju tat- taħlita ta ’ ribavirin ma ’ interferon alfa- 2b għandha titqies bl- attenzjoni f’ din il- popolazzjoni (ara sezzjonijiet 4. 1, 4. 4 u 4. 8).
Study results are summarized in Table 5.
Riżultati ta ’ l- istudju qegħdin imqassra f’ Tabella 5
Virological response in previously untreated paediatric patients IntronA 3 MIU/m2 3 times a week + ribavirin 15 mg/kg/day
IntronA 3 MIU/ m2 3 darbiet fil- ġimgħa ribavirin 15 mg/ kg/ jum
 18 Overall Response1 (n=118)
Rispons Globali1 (n=118)
Genotype 1 (n=92)
Ġenotip 1 (n=92)
Genotype 2/3/4 (n=26) *Number (%) of patients
Ġenotip 2/ 3/ 4 (n=26) * Numru (%) ta ’ pazjenti
Defined as HCV-RNA below limit of detection using a research based RT-PCR assay at end of treatment and during follow-up period
Defimit bħala HCV- RNA taħt il- limitu li jista ’ jitkejjel b’ assay RT- PCR bażat fuq riċerka fl- aħħar tal- kura u waqt il - perijodu ta ’ follow- up
The pharmacokinetics of IntronA were studied in healthy volunteers following single 5 million IU/m2 and 10 million IU doses administered subcutaneously, at 5 million IU/m2 administered intramuscularly and as a 30-minute intravenous infusion.
Il- farmakokinetiċi ta ’ IntronA kienu studjati fuq voluntiera b’ saħħithom wara dożi ta ’ 5 miljun IU/ m² mogħtija taħt il- ġilda, 10 miljun IU mogħtija taħt il- ġilda, 5 miljun IU/ m² mogħtija ġol- muskolu u bħala infużjoni ta ’ 30 minuta ġol- vina.
The mean serum interferon concentrations following subcutaneous and intramuscular injections were comparable.
Il- konċentrazzjonijiet medji ta ’ interferon fis- serum wara l - injezzjonijiet taħt il- ġilda u ġol- muskolu kienu komparabbli.
C max occurred three to 12 hours after the lower dose and six to eight hours after the higher dose.
Is- C max intlaħqet minn tlieta sa 12- il siegħa wara d- doża l- baxxa u minn sitta sa tmien sigħat wara d- doża l- għolja.
The elimination half-lives of interferon injections were approximately two to three hours, and six to seven hours, respectively.
L- eliminazzjoni tal- half lives ta ’ l- injezzjonijiet ta ’ l- interferon kienu ta ’ madwar tnejn sa tliet sigħat, u sitta sa seba ’ sigħat, rispettivament.
Serum levels were below the detection limit 16 and 24 hours, respectively, post-injection.
Il- livelli fis- serum kienu inqas mil- limitu li jistgħu jitkejjlu 16 u 24 siegħa, rispettivament, wara l- injezzjoni.
Both subcutaneous and intramuscular administration resulted in bioavailabilities greater than 100%.
Kemm l- għoti taħt il- ġilda kif ukoll dak ġol- muskolu rriżultaw f’ bijodisponibilità ta ’ aktar minn 100%.
After intravenous administration, serum interferon levels peaked (135 to 273 IU/ml) by the end of the infusion, then declined at a slightly more rapid rate than after subcutaneous or intramuscular administration of medicinal product, becoming undetectable four hours after the infusion.
Wara l- għoti ġol- vina, il- livelli ta ’ l- interferon fis- serum laħqu l- ogħla livell (135 sa 273 IU/ ml) mat - tmiem ta ’ l- infużjoni, imbagħad naqsu b’ rata ftit aktar mgħaġġla milli wara l- għoti tal- prodott mediċinali taħt il- ġilda jew ġol- muskolu, u ma setgħux jitkejjlu aktar erba ’ sigħat wara l- infużjoni.
The elimination half-life was approximately two hours.
L - eliminazzjoni tal- half lives kien ta ’ madwar sagħtejn.
Urine levels of interferon were below the detection limit following each of the three routes of administration.
Il- livelli ta ’ l- interferon fl- awrina kienu anqas mil- limitu li jista ’ jitkejjel wara kull waħda mit- tliet rotot ta ’ kif jingħata.
Multiple-dose pharmacokinetic properties for IntronA injection and ribavirin capsules in children and adolescents with chronic hepatitis C, between 5 and 16 years of age, are summarized in Table 6.
Il- karatteristiċi tal- farmakokinetika ta ’ ħafna dożi għall- injezzjoni IntronA u kapsuli ribavirin fi tfal u adolexxenti b’ epatite Ċ kronika, bejn 5 u 16- il sena, qegħdin imqassra f’ Tabella 6.
The pharmacokinetics of IntronA and ribavirin (dose-normalized) are similar in adults and children or adolescents.
Il- farmakokinetika ta ’ IntronA u ribavirin (normalizzata mad- doża) jixxiebhu fl- adulti u tfal jew adolexxenti.
 19 Table 6.
Tabella 6.
Mean (% CV) multiple-dose pharmacokinetic parameters for IntronA and ribavirin capsules when administered to children or adolescents with chronic hepatitis C
Medja (% CV) tal- parametri farmakokinetiċi b’ ħafna dożi għal IntronA u kapsuli ribavirin meta jingħataw lil tfal jew adolexxenti b’ epatite Ċ kronika IntronA
IntronA
3 MIU/ m2 3 darbiet fil- ġimgħa
15 mg/kg/day as 2 divided doses (n = 17)
15 mg/ kg/ jum bħala 2 dożi (n = 54) maqsuma (n = 17)
1.9 (83)
1. 9 (83)
max (ng/ml) AUC*
3, 275 (25)
3,275 (25) 29,774 (26)
29, 774 (26)
Apparent clearance l/hr/kg
Tneħħija apparenti l/ hr/ kg
0.27 (27)
0. 27 (27)
Not done
Mhux mgħamul
*AUC 12 (ng.hr/ml) for ribavirin; AUC 0-24 (IU.hr/ml) for IntronA
* AUC 12 (ng. hr/ ml) għal ribavirin; AUC 0- 24 (IU. hr/ ml) għal IntronA
Interferon neutralising factor assays were performed on serum samples of patients who received IntronA in Schering-Plough monitored clinical trials.
Fi provi kliniċi taħt is- sorveljanza ta ’ Schering- Plough, assays ta ’ fatturi li jinnewtralizzaw l- interferon saru fuq kampjuni tas- serum ta ’ pazjenti li rċivew IntronA.
Interferon neutralising factors are antibodies which neutralise the antiviral activity of interferon.
Il- fatturi li jinnewtralizzaw l- interferon huma antikorpi li jinnewtralizzaw l- attività antivirali ta ’ l- interferon.
The clinical incidence of neutralising factors developing in cancer patients treated systemically is 2.9% and in chronic hepatitis patients is 6.2%.
L- inċidenza klinika ta ’ fatturi newtralizzanti li jiżviluppaw fil- pazjenti bil- kankru ttrattati sistemikament hi ta ’ 2. 9% u ta ’ 6. 2% fil - pazjenti bl- epatite kronika.
The detectable titres are low in almost all cases and have not been regularly associated with loss of response or any other autoimmune phenomenon.
It- titri li jistgħu jitkejjlu huma baxxi kważi fil- każijiet kollha, u ma kinux assoċjati regolarment ma ’ tnaqqis ta ’ rispons jew ma ’ xi fenomenu awtoimmunitarju ieħor.
In patients with hepatitis, no loss of response was observed apparently due to the low titres.
Fil - pazjenti bl- epatite, l- ebda tnaqqis ta ’ rispons ma ’ kien innutat, milli jidher minħabba t- titri baxxi.
Although interferon is generally recognised as being species specific, toxicity studies in animals were conducted.
Għalkemm l- interferon hu ġeneralment magħruf li huwa speċifiku għall- ispeċi, saru studji dwar it - tossiċità fuq l- annimali.
Injections of human recombinant interferon alfa-2b for up to three months have shown no evidence of toxicity in mice, rats, and rabbits.
Injezzjonijiet ta ’ interferon alfa- 2b rikombinanti uman għal perijodi sa tlett xhur ma wrew l- ebda tossiċità fil- ġrieden, fil- firien u fil- fniek.
Daily dosing of cynomolgus monkeys with 20 x 106 IU/kg/day for 3 months caused no remarkable toxicity.
Doża ta ’ 20 x 106 IU/ kg/ jum għal 3 xhur mogħtija lil xadini tar- razza cynomolgus ma kkawżat ebda tossiċità ta ’ importanza.
Toxicity was demonstrated in monkeys given 100 x 106 IU/kg/day for 3 months.
It- tossiċità dehret fix- xadini li ngħataw 100 x 106 IU/ kg/ kuljum għal 3 xhur.
In studies of interferon use in non-human primates, abnormalities of the menstrual cycle have been observed (see section 4.4).
Fi studji ta ’ l- użu ta ’ l- interferon fi primati mhux umani, anormalitajiet taċ- ċiklu mestruwali kienu innutati (ara sezzjoni 4. 4).
Results of animal reproduction studies indicate that recombinant interferon alfa-2b was not teratogenic in rats or rabbits, nor did it adversely affect pregnancy, foetal development or reproductive capacity in offspring of treated rats.
Ir- riżultati ta ’ studji tar- riproduzzjoni ta ’ l- annimali jindikaw li l- interferon alfa- 2b rikombinanti ma ’ kienx teratoġeniku fil- firien jew fil- fniek, u l- anqas ma kellu xi effett ħażin fuq it- tqala, fuq l- iżvilupp tal- fetu jew fuq il- kapaċità riproduttiva tal- frieħ ta ’ firien li rċivew it- trattament.
Interferon alfa-2b has been shown to have abortifacient effects in Macaca mulatta (rhesus monkeys) at 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2.
L- interferon alfa- 2b intwera li għandu effetti li jwasslu għall- abort fil- Macaca mulatta (xadini tar- razza rhesus) b’ dożi ta ’ 90 u 180 darba iktar minn dik rakkomandata ta ’ 2 miljun IU/ m² ġol- muskolu jew taħt il- ġilda.
Abortion was observed in all dose groups (7.5 million, 15 million and 30 million IU/kg), and was statistically significant versus control at the mid- and high-dose groups (corresponding to 90 and 180 times the recommended intramuscular or subcutaneous dose of 2 million IU/m2).
L- abort kien innutat fil- kategoriji tad- dożi kollha (7. 5 miljuni, 15- il miljun u 30 miljun IU/ kg) u kien statistikament sinifikattiv meta mqabbel mal- kontroll fil- kategoriji tad- doża l- medja u ta ’ dik għolja (li tikkkorrispondi għal 90 u 180 darba iktar mid- doża rakkomandata ta ’ 2 miljun IU/ m² ġol- muskolu jew taħt il- ġilda).
High doses of other forms of interferons alpha and beta are known to produce dose- related anovulatory and abortifacient effects in rhesus monkeys.
Dożi għoljin ta ’ forom oħra ta ’ interferoni alpha u beta huma magħrufa li jipproduċu effetti konnessi mad- doża li jwaqqfu l- ovulazzjoni u li jwasslu għall- abort fix- xadini tar- razza rhesus.
Mutagenicity studies with interferon alfa-2b revealed no adverse events.
Studji dwar il- mutaġeniċità b’ interferon alfa- 2b ma wrew ebda każijiet avversi.
No studies have been conducted in juvenile animals to examine the effects of treatment with interferon alfa-2b on growth, development, sexual maturation, and behaviour (see section 4.4 and Rebetol SPC if IntronA is to be administered in combination with ribavirin).
Ma sarux studji f’ annimali ta ’ età żgħira sabiex jiġu eżaminati l- effetti tal- kura b’ interferon alfa- 2b fuq it- tkabbir, żvilupp, maturazzjoni sesswali, u imġieba (ara sezzjoni 4. 4 u l- SPC ta ’ Rebetol jekk IntronA ikun ser jingħata ma ’ ribavirin).
Glycine, Disodium phosphate anhydrous, Sodium dihydrogen phosphate monohydrate,
Glycine, disodium phosphate anhydrous, sodium phosphate monobasic, soluzzjoni ta ’ l- albumina tal- bniedem.
Solvent: water for injections
Solvent: ilma għall- injezzjonijiet
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn ħlief dawk imsemmija f ’ sezzjoni 6. 6.
An immediate use is recommended.
Huwa rakkomandat li jintuża mill- ewwel.
However, the chemical and physical in-use stability has been demonstrated for 24 hours at 25ºC.
Madankollu, l- istabilità kimika u fiżika waqt l- użu intweriet għal 24 siegħa f’ 25ºC.
Store in a refrigerator (2°C – 8°C).
Aħżen fi friġġ (2C – 8C).
Do not freeze.
Aħżen fil- friża.
Within its shelf-life, for the purpose of transport and/or to facilitate ambulatory use the non- reconstituted product can be kept at or below 25°C for a period up to four weeks before use.
Fil- perijodu ta ’ meta jkun għadu tajjeb, għal skopijiet ta ’ trasport u/ jew biex jitħaffef l- użu ambulatorju, il- prodott mhux rikostitwit jista ’ jinżamm f’ temperatura ta ’ 25°C jew anqas għal perijodu ta ’ mhux aktar minn erba ’ ġimgħat qabel l- użu.
If the product is not reconstituted during the four-week period, it cannot be put back in the refrigerator for a new storage period and must be discarded.
Jekk il- prodott ma jkunx rikostitwit matul il- perijodu ta ’ erba ’ ġimgħat, ma jistax jitpoġġa lura fil- friġġ għal perijodu ġdid ta ’ ħażna u għandu jintrema.
24 mg of powder (corresponding to 1 MIU) in a vial (type I glass), with a stopper (butyl rubber) in a flip-off seal (aluminium) with a bonnet (polypropylene) and 1 ml water for injections in an ampoule (type I glass) with 1 injection syringe, 2 injection needles and 1 cleansing swab.
24 mg ta ’ trab (li jikkorrispondi għal 1 MIU) f’ kunjett (type I glass), b’ tapp (lasktu tal- butyl) f’ siġill li tiftħu b’ saba (aluminium) b’ bonit (polypropylene) u ml 1 ilma għall- injezzjonijiet f’ ampulla (ħġieġ tat- tip I) b’ siringa 1 għall- injezzjoni, 2 labar ta ’ l- injezzjoni u tajjara għat- tindif.
Pack sizes of 1 or 12.
Pakketti ta ’ daqsijiet b’ 1 jew 12.
Not all dosage forms and strengths are appropriate for some indications.
Mhux il- forom kollha tad- dożaġġi u qawwiet ikunu xierqa għal xi indikazzjonijiet.
Please make sure to select an appropriate dosage form and strength.
Jekk jogħġbok kun żgur li tgħażel il- forma tad- dożaġġ u qawwa xierqa.
Reconstitution of IntronA, powder for solution for injection or infusion, for parenteral administration:
Rikostituzzjoni ta ’ IntronA, trab li jinħall f’ likwidu għall- injezzjoni jew infużjoni, biex jingħata b’ injezzjoni:
IntronA is supplied as a powder at strengths of 1 million IU/ml for single-dose use.
IntronA hu pprovdut bħala trab b’ qawwa ta ’ 1 miljun IU/ ml għall- użu f’ doża waħda.
Vials must be reconstituted with 1 ml of water for injections.
Il - kunjetti jridu jkunu rrikostitwiti b’ 1 ml ta ’ ilma għall- injezzjonijiet.
The reconstituted solutions are isotonic for parenteral administration.
Is- soluzzjonijiet rrikostitwiti huma iżotoniċi biex jingħataw b’ injezzjoni.
Proper precautions should be taken during reconstitution to prevent microbial contamination (refer to package leaflet).
Prekawzjonijiet xierqa għandhom jittieħdu waqt ir- rikostituzzjoni sabiex jiġi evitat li jkun hemm kontaminazzjoni b’ mikrobi (irreferi għall- fuljett ta ’ tagħrif).
Using a sterilised injection syringe and injection needle, inject 1 ml water for injections into the vial of IntronA.
Permezz ta ’ siringa u labra għall- injezzjoni sterilizzati, injetta 1 ml ta ’ ilma għall- injezzjonijiet ġol - kunjett ta ’ IntronA.
Agitate gently to facilitate complete dissolution of the powder.
Ċaqlaq it- taħlita bil- mod biex tgħin lit- trab jinħall għal kollox.
The appropriate dose can then be withdrawn with a sterile injection syringe and injected.
Id- doża l- korretta tista ’ mbagħad tinġibed b’ siringa ta ’ l- injezzjoni sterili u tkun injettata.
As for all parenteral medicinal products, inspect the reconstituted solution visually for particulate matter and discolouration prior to administration.
Bħal f’ kull prodott mediċinali li jingħata b’ injezzjoni, is- soluzzjoni rikostitwita għandha tkun miflija għal xi frak u għal telf ta ’ kulur qabel tingħata.
The reconstituted solution should be clear and colourless.
Is- soluzzjoni rikostiwita għandha tkun ċara u bla kulur.
Detailed instructions for the subcutaneous use of the product are provided with the package leaflet (refer to “How to self inject IntronA”).
Istruzzjonijiet dettaljati dwar l- użu għal taħt il- ġilda tal- prodott qed jingħataw fil- fuljett ta ’ tagħrif (irreferi għal “ Kif tinjetta lilek innifsek b’ IntronA ”).
 21 Preparation of IntronA for intravenous infusion:
Preparazzjoni ta ’ IntronA għall- infużjoni fil- vini:
The infusion must be prepared immediately prior to use.
L- infużjoni għandha tkun ippreparata immedjatament qabel l- użu.
The lyophilised powder form of IntronA is to be reconstituted by adding 1 ml of water for injections to the vial.
It- trab fl- għamla li tinħall malajr ta ’ IntronA jrid ikun rikostitwit biż- żieda ta ’ 1 ml ta ’ ilma għall- injezzjonijiet fil- kunjett.
The calculated amount of interferon for the appropriate dose then is withdrawn from the vial(s), added to 100 ml of 9 mg/ml (0.9%) sodium chloride solution for injection and administered over 20 minutes.
L- ammont ikkalkolat għad- doża korretta ta ’ l - interferon ikun mbagħad miġbud mill- kunjett/ i, miżjud ma ’ 100 ml ta ’ 9mg/ ml (0. 9%) sodium chloride soluzzjoni għall- injezzjoni u mogħti fuq medda ta ’ 20 minuta.
Final concentration of interferon in sodium chloride solution must not be less than 1 x 105 IU/ml.
Il- konċentrazzjoni finali ta ’ l - interferon fis- soluzzjoni tas- sodium chloride m’ għandhiex tkun anqas minn 1 x 105 IU/ ml.
NO OTHER MEDICINAL PRODUCT CAN BE INFUSED CONCOMITANTLY WITH INTRONA.
L- EBDA PRODOTT MEDIĊINALI IEĦOR M’ GĦANDU JITĦALLAT MA ’ L- INFUŻJONI TA ’ INTRONA.
Any unused product must be discarded after withdrawal of the dose.
Kwalunkwe prodott li ma jintużax għandu jintrema wara li titwaqqaf id- doża.
SP Europe 73, rue de Stalle B-1180 Bruxelles Belgium
SP Europe 73, rue de Stalle B- 1180 Bruxelles Il- Belġju
9 March 2000 Date of last renewal:
9 ta ’ Marzu 2000 Data ta ’ l- aħħar tiġdid:
23 May 2005
23 Mejju 2005
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu/
Informazzjoni dettaljata dwar dan il- prodott mediċinali tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
 22 1.
1.
IntronA 3 million IU/ml powder and solvent for solution for injection or infusion
IntronA 3 miljun IU/ ml trab u solvent għal soluzzjoni għall- injezzjoni jew infużjoni
One vial of powder contains 3 million IU of interferon alfa-2b produced in E.coli by recombinant DNA technology.
Kull kunjett ta ’ trab fih 3 miljun IU ta ’ interferon alfa- 2b mgħamul fl- E. coli bit- teknoloġija ta ’ DNA rikombinanti.
After reconstitution, 1 ml contains 3 million IU of interferon alfa-2b.
Meta jkun rikostitwit, 1 ml jkun fih 3 miljun IU ta ’ interferon alfa- 2b.
Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis B viral replication (presence of HBV-DNA and HBeAg), elevated alanine aminotransferase (ALT) and histologically proven active liver inflammation and/or fibrosis.
It- trattament ta ’ pazjenti adulti li għandhom l- epatite B kronika assoċjata ma ’ evidenza ta ’ replikazzjoni virali ta ’ l- epatite B (preżenza ta ’ HBV- DNA u HBeAg), alanine aminotransferase (ALT) elevat u infjammazzjoni u/ jew fibrożi attiva fil- fwied li tkun konfermata b' mod istoloġiku.
The best way to use IntronA in th is indication is in combination with ribavirin.
L- aħjar mod kif tuża IntronA f’ din l- indikazzjoni huwa flimkien ma ’ ribavirin.
Treatment of adult patients with Philadelphia chromosome or bcr/abl translocation positive chronic myelogenous leukaemia.
It- trattament ta ’ pazjenti adulti li għandhom il- lewkimja tal- mudullun kronika tal - kromosoma ta ’ Philadelphia jew lewkimja kronika majeloġena pożittiva għat- traslokazzjoni bcr/ abl.
Clinical experience indicates that a haematological and cytogenetic major/minor response is obtainable in the majority of patients treated.
L- esperjenza klinika tindika li rispons maġġuri/ minuri ematoloġiku u ċitoġenetiku jtista ’ jinkiseb fil - maġġoranza tal- pazjenti ttrattati.
 23 Combination therapy:
Terapija kombinata:
As adjuvant therapy in patients who are free of disease after surgery but are at high risk of systemic recurrence, e.g., patients with primary or recurrent (clinical or pathological) lymph node involvement.
Bħala terapija aġġuntiva f’ pazjenti li huma ħielsa mill- mard wara l- kirurġija iżda li jinsabu f’ riskju kbir li jirkadu b’ mod sistematiku, eż., pazjenti b’ involviment primarju jew rikorrenti (kliniku jew patoloġiku) tan- nodi limfatiċi.
The administered dose should be reduced by 50% in case of occurrence of haematological disorders (white blood cells < 1,500/mm3, granulocytes < 1,000/mm3, thrombocytes < 100,000/mm3).
Id- doża mogħtija għanda titnaqqas b’ 50% f' każ li jseħħu problemi ematoloġiċi (ċelluli bojod tad - demm < 1, 500/ mm3, granuloċiti < 1, 000/ mm3, tromboċiti < 100, 000/ mm3).
Treatment should be discontinued in case of severe leukopaenia (< 1,200/mm3), severe neutropaenia (< 750/mm3) or severe thrombocytopaenia (< 70,000/mm3).
It- trattament għandu jitwaqqaf f’ każijiet ta ’ lewkopenja severa (< 1, 200/ mm3), ta ’ newtropenja severa (< 750/ mm3) jew ta ’ tromboċitopenija severa (< 70, 000/ mm3).
Interferon alfa-2b 3 MIU/m2 is administered subcutaneously 3 times a week (every other day) in combination with ribavirin capsules or oral solution administered orally in two divided doses daily with food (morning and evening).
Interferon alfa- 2b 3 MIU/ m2 jingħata taħt il- ġilda tliet darbiet fil- ġimgħa (darba kull jumejn) flimkien mal- kapsuli ribavirin jew soluzzjoni orali li tittieħed mill- ħalq maqsuma f’ żewġ dożi kuljum ma ’ l- ikel (filgħodu u filgħaxija).
 24 (See ribavirin capsule SPC for dose of ribavirin capsules and dosage modification guidelines for combination therapy.
(Ara l- SPC tal- kapsuli ribavirin u l- linji gwida għal tibdil fid- dożaġġ għal terapija kombinata.
Treatment should be continued for another 6-month period (i.e., a total of 12 months) in patients who exhibit negative HCV-RNA at month 6, and with viral genotype 1 (as determined in a pre-treatment sample) and high pre-treatment viral load.
It- trattament għandu jitkompla għal perijodu ieħor ta ’ 6 xhur (i. e., għal total ta ’ 12- il xahar) f’ pazjenti li juru HCV- RNA negattiv f’ xahar 6, u b’ ġenotip virali 1 (kif stabbilit f’ kampjun ta ’ qabel it - trattament) u b’ viral load għoli qabel it- trattament.
Genotype 2/3:
Ġenotip 2/ 3:
Virological responses after 1 year of treatment and 6 months of follow-up were 36% for genotype 1 and 81% for genotype 2/3/4.
Rispons viroloġiku wara sena 1 ta ’ trattament u 6 xhur follow- up kienu ta ’ 36% għall- ġenotip 1 u 81% għall- ġenotip 2/ 3/ 4.
The recommended dosage is 2 million IU/m2 administered subcutaneously three times a week (every other day) for both splenectomised and non-splenectomised patients.
Id- dożaġġ rakkomandat huwa ta ’ 2 miljun IU/ m2 mogħti taħt il- ġilda tliet darbiet fil- ġimgħa (darba kull jumejn) kemm għall- pazjenti splenektomizzati kif ukoll għal dawk li mhumiex.
 25 Chronic Myelogenous Leukaemia:
Lewkimja tal- Mudullun Kronika:
The recommended dosage of IntronA is 4 to 5 million IU/m2 administered daily subcutaneously.
Id- dożaġġ rakkomandat ta ’ IntronA hu ta ’ 4 sa 5 miljun IU/ m2 mogħtija kuljum taħt il- ġilda.
Some patients have been shown to benefit from IntronA 5 million IU/m2 administered daily subcutaneously in association with cytarabine (Ara-C) 20 mg/m2 administered daily subcutaneously for 10 days per month (up to a maximum daily dose of 40 mg).
Intwera li xi pazjenti bbenefikaw minn 5 miljun IU/ m2 IntronA mogħtija kuljum taħt il- ġilda flimkien ma ’ 20 mg/ m2 cytarabine (Ara- C) mogħtija kuljum taħt il- ġilda għal 10 ijiem kull xahar (sa doża massima ta ’ 40 mg kuljum).
When the white blood cell count is controlled, administer the maximum tolerated dose of IntronA (4 to 5 million IU/m2 daily) to maintain haematological remission.
Meta l- għadd taċ- ċelluli bojod fid- demm ikun ikkontrollat, agħti d- doża massima tollerata ta ’ IntronA (4 sa 5 miljun IU/ m2 kuljum) biex ikun sostnut it- titjib ematoloġiku.
In patients who are in the plateau phase (more than 50% reduction of myeloma protein) following initial induction chemotherapy, interferon alfa-2b may be administered as monotherapy, subcutaneously, at a dose of 3 million IU/m2 three times a week (every other day).
Fil- pazjenti li jinsabu fil- fażi ta ’ stabbiltà (aktar minn 50% tnaqqis tal- proteina tal- majeloma) wara kemoterapija ta ’ l- induzzjoni inizjali, interferon alfa- 2b jista ’ jingħata bħala monoterapija, taħt il- ġilda, f’ doża ta ’ 3 miljun IU/ m2 tliet darbiet fil- ġimgħa (darba kull jumejn).
As induction therapy, interferon alfa-2b is administered intravenously at a dose of 20 million IU/m2 daily for five days a week for a four-week period; the calculated interferon alfa-2b dose is added to sodium chloride 9 mg/ml (0.9%) solution for injection and administered as a 20- minute infusion (see section 6.6).
Bħala terapija ta ’ l- induzzjoni, l- interferon alfa- 2b jingħata ġol- vina b’ doża ta ’ 20 miljun IU/ m² kuljum għal ħamest ijiem fil- ġimgħa għal perijodu ta ’ erba ’ ġimgħat; id- doża kkalkulata ta ’ interferon alfa- 2b tiżdied ma ’ sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni u tingħata bħala infużjoni ta ’ 20 minuta (ara sezzjoni 6. 6).
As maintenance treatment, the recommended dose is 10 million IU/m2 administered subcutaneously three days a week (every other day) for 48 weeks.
Bħala trattament ta ’ manteniment, id- doża rakkomandata hi 10 miljun IU/ m² mogħtija taħt il- ġilda tliet darbiet fil- ġimgħa (darba kull jumejn) għal 48 ġimgħa.
If severe adverse events develop during interferon alfa-2b treatment, particularly if granulocytes decrease to < 500/mm3 or alanine aminotransferase/aspartate aminotransferase (ALT/AST) rises to > 5 x upper limit of normal, discontinue treatment temporarily until the adverse event abates.
Jekk iseħħu każijiet avversi severi matul it- trattament b’ interferon alfa- 2b, speċjalment jekk il - granuloċiti jonqsu għal < 500/ mm³ jew l- alanine aminotransferase/ aspartate aminotransferase (ALT/ AST) jogħlew għal > 5 darbiet l- ogħla limitu tan- normal, waqqaf it- trattament b' mod temporanju sakemm il- każ avvers ibatti.
If intolerance persists after dose adjustment or if granulocytes decrease to < 250/mm3 or ALT/AST rises to > 10 x upper limit of normal, discontinue interferon alfa-2b therapy.
Jekk l- intolleranza tippersisti wara l- aġġustament fid- doża jew jekk il - granuloċiti jonqsu għal < 250/ mm³ jew l- ALT/ AST jogħlew għal > 10 darbiet l- ogħla limitu tan - normal, waqqaf it- terapija b’ interferon alfa- 2b.
- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure,
- Passat ta ’ mard tal- qalb sever li kien jeżisti minn qabel, eż., insuffiċjenza tal- qalb konġestiva
- Epilepsy and/or compromised central nervous system (CNS) function (see section 4.4).
- Epilessija u/ jew funzjoni kompromessa tas- sistema nervuża ċentrali (CNS) (ara sezzjoni 4. 4)
 26 Children and adolescents:
Tfal u adolexxenti:
As in adult patients, children and adolescents experienced other psychiatric adverse events (e.g., depression, emotional lability, and somnolence).
Bħal f’ pazjenti adulti, tfal u adolexxenti kellhom każijiet avversi oħra (eż dipressjoni, burdati emozzjonali, u ngħas).
Other CNS effects including aggressive behaviour (sometimes directed against others), bipolar disorders, mania, confusion and alterations of mental status have been observed with alpha interferons.
Effetti oħra fuq is- CNS inkluż imġieba aggressiva (kultant indirizzata lejn l - oħrajn), konfużjoni u tibdil fl- istat mentali dehru b’ alpha interferons.
Patients should be closely monitored for any signs or symptoms of psychiatric disorders.
Il- pazjenti għandhom ikunu monitorati mill- qrib għal kwalunkwe sinjali jew sintomi ta ’ disturbi psikjatriċi.
If such symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the prescribing physician and the need for adequate therapeutic management should be considered.
Jekk jidhru dawn is - sintomi, is- serjetà li jista ’ jkollhom dawn l- effetti għandha titqies mit- tabib li jkun qed jordnhom u l - ħtieġa ta ’ maniġġar terapewtiku xieraq għandha tkun ikkunsidrata.
Acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon alfa-2b have been observed rarely during IntronA therapy.
Reazzjonijiet ta ’ sensittività eċċessiva akuta (eż. urtikarja, anġjoedima, bronkokostrizzjoni, anafilassi) għall- interferon alfa- 2b dehru f’ każijiet rari waqt it- terapija b’ IntronA.
IntronA must be used cautiously in patients with debilitating medical conditions, such as those with a history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to ketoacidosis.
IntronA għandu jintuża b’ attenzjoni f’ pazjenti b’ kundizzjonijiet mediċi ta ’ indeboliment, bħal dawk b’ passat mediku ta ’ mard pulmonari (eż., mard pulmonari ostruttiv kroniku) jew dijabete mellitus suxxettibbli għall- ketoaċidożi.
Caution must be observed also in patients with coagulation disorders (e.g., thrombophlebitis, pulmonary embolism) or severe myelosuppression.
Attenzjoni għandha wkoll tingħata lill- pazjenti bi problemi ta ’ koagulazzjoni (eż., tromboflebite, emboliżmu pulmonari) jew majelosuppressjoni serja.
 27 Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA.
Infiltrazzjonijiet pulmonarji, pulmonite, u pnewmonja, li kultant wasslu għall- mewt, kienu innutati f’ każijiet rari fil- pazjenti ttrattati bl- interferon alpha, inklużi dawk ittrattati b’ IntronA.
Adult patients with a history of congestive heart failure, myocardial infarction and/or previous or current arrhythmic disorders, who require IntronA therapy, must be closely monitored.
Pazjenti b’ passat mediku ta ’ insuffiċjenza tal- qalb konġestiva, infarti mijokardjali u/ jew problemi arritmiċi passati jew attwali, li jeħtieġu t- terapija b’ IntronA, għandhom ikunu segwiti mill- qrib.
It is recommended that those patients who have pre-existing cardiac abnormalities and/or are in advanced stages of cancer have electrocardiograms taken prior to and during the course of treatment.
Huwa rakkomandat li dawk il- pazjenti li għandhom anormalitajiet kardijaċi li kienu jeżistu minn qabel u/ jew jinsabu fi stadju avanzat ta ’ kankru jieħdu elettrokardjogrammi qabel u matul il- kors tat- trattament.
 28 Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived albumin.
Tilqim xieraq (Epatite A u B) għandu jkun konsidrat għal pazjenti li jirċievu b’ mod regolari/ ripetut albumina li tkun ġejja mill- plażma tal- bniedem.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses.
Miżuri standard biex jiġu evitati infezzjonijiet li jiġu mill- użu ta ’ prodotti mediċinali li jkunu preparati mid- demm jew plażma tal- bniedem inkluż l- għażla tad- donaturi, screening tad- donazzjonijiet individwali u ġabra tal- plażma għal markaturi speċifiċi ta ’ l- infezzjoni u l- inklużjoni ta ’ passi effettivi fil- manifattura għall- inattivazzjoni/ tneħħija ta ’ viruses.
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 dwar l- epatite Ċ kronika saritilhom bijopsija tal- fwied qabel ma kienu inklużi, iżda f’ ċerti każijiet (jiġifieri l- pazjenti bil- ġenotipi 2 u 3), it- trattament jista ’ jkun possibbli mingħajr konferma istoloġika.
If thyroid abnormalities are detected, the patient’s thyroid status should be evaluated and treated as clinically appropriate.
Jekk jinsabu anormalitajiet tat- tirojde, l- istat tat- tirojde tal - pazjent għandu jiġi evalwat u kkurat kif ikun xieraq b’ mod kliniku.
A general reversal of these trends was noted during the 6 months follow-up post treatment.
Kien nutat li dawn it- tendenzi reġgħu lura b’ mod ġenerali waqt is- 6 xhur ta ’ follow- up wara l- kura.
However, based on interim data from a long-term follow-up study, 12 (14%) of 84 children had a > 15 percentile decrease in rate of linear growth, of whom 5 (6%) children had a > 30 percentile decrease despite being off treatment for more than 1 year.
Madankollu, minn dejta interim minn studju ta ’ follow- up fuq perijodu twil, 12 (14%) ta ’ l- 84 tfal kellhom > 15 perċentwali fir- rata ta ’ tkabbir linejari, li minnhom 5 (6%) tat- tfal kellhom tnaqqis ta ’ > 30 perċentwali minkejja li kienu waqqfu l- kura għal aktar minn sena.
Therefore, the risk/benefit of the combined use of interferon alfa-2b and
Minbarra hekk, riżultati ta ’ qabel l- użu kliniku dwar tossiċità fiż- żgħażagħ wrew tnaqqis minuri, relatat mad- doża fit- tkabbir globali fil- firien tat- twelid li ngħataw ribavirin (ara sezzjoni 5. 3).
 29 ribavirin should be assessed in young children prior to the initiation of therapy.
Għalhekk ir- riskju/ benefiċċju ta ’ l - użu kombinat ta ’ interferon alfa- 2b u ribavirin għandu jiġi evalwat fi tfal żgħar qabel tinbeda t - terapija.
HCV/HIV Coinfection:
Ko- infezzjoni bl- HCV/ HIV:
Administration of IntronA in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration), which may be life-threatening or fatal as a result of the concomitantly administered medicinal product.
L- għoti ta ’ IntronA flimkien ma ’ sustanzi kemoterapewtiċi oħra (eż., Ara- C, cyclophosphamide, doxorubicin, teniposide) jista ’ jwassal għal riskju akbar ta ’ tossiċità (severità u żmien), li jista ’ jkun ta ’ theddida għall- ħajja jew fatali minħabba l- prodott mediċinali li jkun ingħata miegħu.
If ALT flares during IntronA therapy to greater than or equal to 2 times baseline, IntronA therapy may be continued unless signs and symptoms of liver failure are observed.
Jekk matul it- terapija b’ IntronA l- ALT jogħla f’ daqqa u jilħaq jew jaqbeż id- doppju tal- livelli bażi, it- terapija b’ IntronA tista ’ titkompla sakemm ma jkunux innutati sinjali u sintomi ta ’ indebolimet qawwi tal- fwied.
Interferons may affect the oxidative metabolic process.
L- interferoni jistgħu jaffettwaw il- proċess metaboliku ossidattiv.
This must be considered during concomitant therapy with medicinal products metabolised by this route, such as the xanthine derivatives
Dan għandu jkun ikkunsidrat waqt terapija konkomitanti ma ’ prodotti mediċinali li jkunu metabolati permezz ta ’ din ir- rotta, bħal ma huma d- derivattivi ta ’ xanthine, theophylline jew aminophylline.
Administration of IntronA in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration) (see section 4.4).
L- għoti ta ’ IntronA flimkien ma ’ sustanzi kemoterapewtiċi oħra (eż., Ara- C, cyclophosphamide, doxorubicin, teniposide) jista ’ jwassal għal riskju akbar ta ’ tossiċità (severità u żmien) (ara sezzjoni 4. 4).
In clinical trials conducted in a broad range of indications and at a wide range of doses (from 6 MIU/m2/week in hairy cell leukaemia up to 100 MIU/m2/week in melanoma), the most commonly reported undesirable effects were fever, fatigue, headache and myalgia.
Fi provi kliniċi magħmula fuq firxa wiesgħa ta ’ indikazzjonijiet u b’ medda wiesgħa ta ’ dożi (minn 6 MIU/ m²/ ġimgħa għal- lewkimja tal- hairy cell sa 100 MIU/ m²/ ġimgħa għall- melanoma), l- aktar effetti mhux mixtieqa li kienu rrappurtati ta’ spiss kienu d- deni, għeja kbira, uġigħ ta ’ ras u uġigħ fil- muskoli.
In Table 1 the frequency of patients reporting (treatment related) undesirable effects is presented from clinical trials in naïve patients treated for one year.
F’ Tabella 1 il- frekwenza ta ’ pazjenti li rrappurtaw effetti mhux mixtieqa (konnessi mat- trattament) huma elenkati minn provi kliniċi f’ pazjenti naive ittrattati għal sena.
The adverse reactions listed in Table 1 are based on experience from clinical trials and post-
Ir- reazzjonijiet avversi elenkati f’ Tabella 1 huma bbażati fuq l- esperjenza minn provi kliniċi u ta ’ wara t- tqegħid fis- suq.
Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: very common (≥1/10); common (≥1/100, < 1/10); uncommon (≥1/1,000, < 1/100); rarely (≥1/10,000, < 1/1,000); very rarely (< 1/10,000); not known.
Fost il- klassijiet tas- sistemi ta ’ l- organi, ir - reazzjonijiet avversi huma elenkati taħt it- titli tal- frekwenza skond il- kategoriji li ġejjin: komuni ħafna (≥1/ 10); komuni (≥1/ 100, < 1/ 10); mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000); mhux magħruf.
Psychiatric disorders§
Disturbi psikjatriċi§
Vision blurred Conjunctivitis, vision abnormal, lacrimal gland disorder, eye pain
Disturbi fil- widnejn u fis- sistema labirintika
Retinal haemorrhages§, retinopathies (including macular oedema), retinal artery or vein obstruction§, optic neuritis, papilloedema, loss of visual acuity or visual field, cotton-
Vista mċajpra Konġuntivite, vista anormali, disturbi fil- glandola tad - dmugħ, uġigħ fl- għajnejn Emoraġġiji fir- retina§, retinopatiji (inkluża edema makulari), ostruzzjoni fl- arterja jew vina tar- retina§, nevrite ottika, papilledema, tnaqqis fl- akutezza viżiva jew kamp viżiv, tikek qieshom tajjar§
wool spots§ Ear and labyrinth Common:
Komuni:
*These events were only common with IntronA alone § See section 4.4
* Dawn il- każijiet kienu komuni biss b’ IntronA waħdu § Ara sezzjoni 4. 4
Table 2 Adverse reactions very commonly and commonly reported in paediatric clinical trials Very common (≥1/10) - Common (≥1/100, < 1/10) System Organ Class  Infection and infestations
Reazzjonijiet avversi irrapurtati b’ mod komuni ħafna u komuni fil- provi kliniċi pedjatriċi Komuni ħafna (≥1/ 10) - Komuni (≥1/ 100, < 1/ 10)
Nervous system disorders§
Disturbi fis- sistema nervuża§
Arthralgia, myalgia, musculoskeletal pain
Artralġja, mijalġja, uġigħ muskolskeletali
Enuresis, micturition disorder, urinary incontinence
Disturbi fis- sistema riproduttiva u fis- sider
 Reproductive system and breast disorders
Enureżi, disturbi ta ’ l- awrina, inkontinenza ta ’ l- awrina
 36 The results of several studies suggest that, once bound to the cell membrane, interferon initiates a complex sequence of intracellular events that include the induction of certain enzymes.
Ir- riżultati ta ’ diversi studji jissuġġerixxu li, hekk kif ikun mqabbad mal- membrana taċ- ċellula, l - interferon jagħti bidu għal sekwenza kumplessa ta ’ okkorrenzi intraċellulari li jinkludu l- induzzjoni ta ’ ċerti enżimi.
Response rates in these trials were increased with compliance.
Ir- rati ta ’ rispons f’ dawn il- provi kienu ogħla meta l- pazjenti kienu konformi mal- kura.
 37 sustained response 6 months after 1 year of treatment than those who took < 80% of their treatment (56% vs.
Irrispettiv mill - ġenotip, il- pazjenti li rċivew IntronA flimkien ma ’ ribavirin u rċivew ≥ 80% tat- trattament tagħhom kellhom rispons sostnut ogħla 6 xhur wara sena ta ’ trattament minn dawk li ħadu < 80% tat- trattament tagħhom (56% vs.
Sustained virological response based on genotype ribavirin versus pegylated interferon alfa-2b in HCV/HIV co-infected patients
Rispons viroloġiku sostnut ibbażat fuq il- ġenotip wara IntronA flimkien ma ’ ribavirin kontra interferon alfa- 2b pegilat flimkien ma ’ ribavirin f’ pazjenti ko- infettati b’ HCV/ HIV Studju 11 Studju 22 interferon alfa- 2b pegilat( 100 interferon jew 150c
pegylated
alfa- 2b pegilat (1. 5 µg/ kg /
alfa-2b (100
µg/ ġimgħa) +