qanastek/EMEA-V3 huggingface dataset:
Adverse events were experienced by 88% of Pegasys-treated patients as compared with 53% of patients in the lamivudine comparator group, while 6% of the Pegasys-treated and 4% of the lamivudine-treated patients experienced serious adverse events during the studies.
Avvenimenti avversi dehru fi 88% tal- pazjenti kkurati b’ Pegasys meta mqabbel ma ’ 53% tal- pazjenti fil- grupp ta ’ paragun b’ lamivudine, filwaqt li 6% tal- pazjenti kkurati b’ Pegasys u 4% tal - pazjenti kkurati b’ lamivudine esperjenzaw episodji avversi serji waqt l- istudji.
The percentage of patients with
Avvenimenti avversi jew anormalitajiet tal- laboratorju wasslu għal twaqqif tal- kura b’ Pegasys f’ 5% tal- pazjenti, filwaqt li anqas minn 1% tal- pazjenti waqfu mill- kura b’ lamivudine għal dawn ir- raġunijiet.
64 cirrhosis who withdrew from treatment was similar to that of the overall population in each treatment group.
Il- persentaġġ ta ’ pazjenti b’ ċirrożi li waqfu mill- kura kien simili għal dak tal- popolazzjoni globali f’ kull grupp ta ’ kura.
Table 4 summarises the undesirable effects reported with Pegasys monotherapy in CHB or CHC patients and with Pegasys in combination with ribavirin in CHC patients.
Tabella 4 tiġbor l- effetti mhux mixtieqa rrappurati b’ monoterapija ta ’ Pegasys f’ pazjenti b’ CHB u jew CHC u b’ Pegasys f’ taħlita flimkien ma ’ ribavirin f’ pazjenti b’ CHC.
Table 4:
65 Tabella 4:
Aplastic anemia
Panċitopenja
Very rare < 1/ 10,000
Anemija aplastika
Anaphylaxis, systemic lupus erythematosus rheumatoid arthritis
Anafilassi, lupus erythematosus sistemika, artrite rewmatojda
Coma, convulsions, facial palsy
Koma, konvulżjonijiet, paralisi fil- wiċċ
Optic neuropathy, Papilledema, retinal vascular disorder, retinopathy, corneal ulcer
Newropatija ottika, Telf tal- vista papilledima, disturbi vaskulari fir- retina, retinopatija, ulċera tal- korneja
66 Body system
66 Sistema tal - ġisem Disturbi fil- qalb
Common ≥ 1/ 100 to < 1/ 10
Komuni ≥ 1/ 100 sa < 1/ 10 Takikardja, palpitazzjonijiet, edima periferali
Rare ≥ 1/ 10,000 to < 1/ 1000
Rari ≥ 1/ 10, 000 sa < 1/ 1000 Infart mijokardijaku, insuffiċjenza tal- qalb konġestiva, anġina, takikardja supraventrikolari, arritmija, fibrillazzjoni atrijali, perikardite, kardjomijopatija
Diarrhoea*, nausea*, abdominal pain*
Dijarea *, tqalligħ *, uġigħ addominali
Rash, sweating increased, psoriasis, urticaria, eczema, skin disorder, photosensitivity reaction, night sweats
Raxx, żieda fl - għaraq, psorjażi, urtikarja, ekżema, disturbi fil- ġilda, reazzjoni ta ’ fotosensittività, tgħereq ħafna matul il- lejl
General disorders Pyrexia, and rigors*, administration pain*, site conditions asthenia, fatigue, injection site reaction*, irritability*
Disturbi ġenerali Deni *, u kondizzjonijiet rogħda *, ta 'mnejn uġigħ, jingħata astenja, għeja, reazzjoni fis- sit ta ’ l - injezzjoni *, irritabilità *
67 Post marketing adverse events
Avvenimenti avversi rrapportati wara t- tqegħid fis- suq
However in neither disease was this correlated with lack of therapeutic response.
Madanakollu, dan ma kienx ikkorrelat ma ’ nuqqas ta ’ effett terapewtiku fl- ebda marda.
Laboratory values for HIV-HCV co-infected patients Although haematological toxicities of neutropenia, thrombocytopenia and anaemia occurred more frequently in HIV-HCV patients, the majority could be managed by dose modification and the use of growth factors and infrequently required premature discontinuation of treatment.
68 Figuri tal- laboratorju f’ pazjenti ko- infettati b’ HIV- HCV Għalkemm tossiċitajiet ematoloġiċi ta ’ newtropenja, tromboċitopenja u anemija seħħew aktar ta ’ spiss f’ pazjenti b’ HIV- HCV, il- maġġoranza setgħet tiġi kkontrollata permezz ta ’ modifikazzjoni fid- doża u l - użu ta ’ fatturi ta ’ tkabbir u f’ każijiet rari kien meħtieġ twaqqif bikri tal- kura.
Interferon alfa-2a is conjugated with bis-[monomethoxy polyethylene glycol] at a degree of substitution of one mole of polymer/ mole of protein. The average molecular mass is approximately 60,000 of which the protein moiety constitutes approximately 20,000.
Il- piż molekulari medju huwa ta ’ madwar 60, 000 li minnu l- parti tal- proteina tikkostitwixxi madwar 20, 000.
The first phase of decline occurs 24 to 36 hours after the first dose of Pegasys is followed by and the second phase of decline which continues over the next 4 to 16 weeks in patients who achieve a sustained response.
L- ewwel fażi tat- tnaqqis tiġri f’ 24 sa 36 siegħa wara l- ewwel doża ta ’ Pegasys u hija segwita mit- tieni fażi tat- tnaqqis li tkompli fl- 4 sa 16 il- ġimgħa ta ’ wara f’ pazjenti li jilħqu rispons sostenut.
Ribavirin had no significant effect on the initial viral kinetics over the first 4 to 6 weeks in patients treated with the combination of ribavirin and pegylated interferon alfa-2a or interferon alfa.
Ribavirin ma kellu l- ebda effettsinifikanti fuq il- kinetiċi virali tal- bidu fl- ewwel 4 sa 6 ġimgħat f’ pazjenti li kienu kkurati bit- taħlita ta ’ ribavirin u pegylated interferon alfa- 2a jew interferon alfa.
A total of 283/ 1351 (21%) of patients had advanced fibrosis or cirrhosis, 85/ 1351 (6%) had cirrhosis.
69 Total ta ’ 283/ 1351 (21%) tal- pazjenti kellhom fibrożi avvanzata jew ċirrożi, 85/ 1351 (6%) kellhom ċirrożi.
69 Table 5:
Tabella 5:
These patients had stable HIV disease and mean CD4 T-cell count was about 500 cells/ µL.
70 Dawn il- pazjenti kellhom marda tal- HIV stabbli u l- għadd medju taċ- ċelloli T CD4 kien ta ’ madwar 500 ċellola/ µL. Għadhom għadejjin provi kliniċi f’ dawk li ma kellhomx rispons u f’ dawk li rkadew.
For HCV monoinfected patients and HIV-HCV co-infected patients, for treatment regimens, duration of therapy and study outcome see Tables 6, 7, 8 and Table 14, respectively.
F’ pazjenti infettati biss b’ HCV u pazjenti ko- infettati b’ HIV- HCV, għad- dożaggi ta ’ kura, tul tat- terpija u riżultati ta ’ l- istudju ara Tabelli 6, 7, 8 u 14, rispettivament.
Virological response was defined as undetectable HCV RNA as measured by the COBAS AMPLICOR™ HCV Test, version 2.0 (limit of detection 100 copies/ ml equivalent to 50 International Units/ ml) and sustained response as one negative sample approximately 6 months after end of therapy.
Rispons. viroloġiku kien iddefinit bħala livell ta ’ HCV RNA li ma jistax jitkejjel, kif imkejjel bit- test COBAS AMPLICOR™ HCV, verżjoni 2. 0 (limitu tal- kejl 100 kopja/ ml ekwivalenti għal 50 Kejl Internazzjonali/ ml) u rispons sostenut li deher bħala kampjun negattiv wieħed madwar 6 xhur wara t- tmiem tat- terapija.
Pegasys Interferon Pegasys Pegasys 180 mcg alfa-2a 180 mcg 180 mcg
Pegasys
Interferon Alfa-2b
Interferon
180 mcg 6 MIU/
180 mcg
3
180 mcg
MIU &
3 MIU
3 MIU
MIU u
Ribavirin Ribavirin 1000/ 1200 1000/ 1200 mg mg
Ribavirin 1000/ 1200 1000/ 1200
(N=701)
mg
(N=478)
(N=444)
(N=444)
(N=436)
48 weeks
ġimgħa 48 ġimgħa ġimgħa Rispons fl - aħħar tal - kura
Response
55- 69%
55 - 69%
22- 28%
Overall Sustained Response
Risponssost enutkomples siv
The results of study NV15942 provide the rationale for recommending treatment regimens based on genotype, baseline viral load and virological response at week 4 (see Tables 1, 7 and 8).
Ir- riżultati ta ’ l- istudju NV15942 jipprovdu r- raġunijiet wara l - għażla tat- tipi ta ’ kuri rakkomandati skond il- ġenotip, viral load fil- linja bażi u r- rispons viroloġiku fir - raba ’ ġimgħa (ara Tabelli 1, 7 u 8).
71 Table 7:
71 Tabella 7:
1000/ 1200 mg 800 mg 1000/ 1200 mg 1000/ 1200 mg
1000/ 1200 mg 1000/ 1200 mg 1000/ 1200
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL *Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 w vs.
Viral load baxxa= ≤ 800, 000 IU/ mL; Viral load għolja= > 800, 000 IU/ mL * Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 ġ vs.
Odds Ratio (95% CI) = 1.52 (1.07 to 2.17) P-value (stratified Cochran-Mantel-Haenszel test) = 0.020 *Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 w vs.
Odds Ratio (95% CI) = 1. 52 (1. 07 sa 2. 17) Valur- p (test Cochran- Mantel- Haenzel stratifikat) = 0. 020 * Pegasys 180 mcg ribavirin 1000/ 1200 mg, 48 ġ vs.
72 Although limited, data indicated that shortening treatment to 24 weeks might be associated with a higher risk of relapse (see Table 9).
72 Għalkemm limitat, it- tagħrif jindika li tqassir tal- kura għal 24 ġimgħa jista ’ jkun assoċjat ma ’ riskju akbar li wieħed jirkadi (ara Tabella 9).
Relapse of Virological Response at the End of Treatment for Rapid Virological Response Population
Rikaduta tar - Rispons Viroloġiku fit- Tmiem tal- Kura għall- Popolazzjoni ta ’ Rispons Viroloġiku Rapidu
Pegasys Pegasys
Studju NV17317 Differenza fil- kura Pegasys
Ribavirin 800 mg 24 weeks
Ribavirin Ribavirin 800 mg 800 mg 24 ġimgħa 16- il ġimgħa - 10. 6% [- 15. 5%; Ġenotip 2 jew 3
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL RVR = rapid viral response (HCV RNA undetectable) at week 4
P=0. 002
73 The data indicated that shortening treatment to 16 weeks is associated with a higher risk of relapse (see Table 11).
Viral load baxxa = ≤ 800, 000 IU/ mL; Viral load għolja = > 800, 000 IU/ mL RVR = rispons virali rapidu (HCV RNA mhux osservat) fir- raba ’ ġimgħa It- tagħrif indika li tqassir tal- kura għal 16- il ġimgħa huwa assoċjat ma ’ riskju ogħla ta ’ rkadar (ara Tabella 11).
Table 11:
73 Tabella 11:
Ribavirin 800 mg 24 weeks
Ribavirin 800 mg 16- il ġimgħa P < 0. 0001 9. 3% [5. 2%; 13. 6%] 6% (23/ 386) 15% (67/ 439) Ġenotip 2 jew 3 RVR P=0. 04 5% [0. 6%; 10. 3%] 1% (2/ 141) 6% (10/ 155) Viral load baxxa P=0. 0002 11. 5% [5. 6%; 17. 4%] 9% (21/ 245) 20% (57/ 284) Viral load għolja
Genotype 2 or 3
Viral load baxxa = ≤ 800, 000 IU/ mL; Viral load għolja = > 800, 000 IU/ mL RVR = rispons virali rapidu (HCV RNA mhux osservat) fir- raba ’ ġimgħa
15%
L- effikaċja superjuri ta ’ Pegasys meta mqabbla ma ’ dik ta ’ interferon alfa- 2a dehret anki bħala rispons istoloġiku, inkluża f’ pazjenti b’ ċirrożi u/ jew ko- infezzjoni b’ HIV- HCV.
6% (23/ 386)
Pazjenti b’ epatite Ċ kronika li ma rrispondewx għall- kura ta ’ qabel
9.3% [5.2%;
Il- gruppi ta ’ kura kollha kellhom perijodu ta ’ wara ta ’ 24 ġimgħa bla kura.
P < 0.0001
Differenzi fir- rispons viroloġiku sostenut ibbażati fuq it- tul u d- demografiċi tal- kura huma mniżżla f’ Tabella 12.
RVR
74 Tabella 12:
(67/ 439)
Globali
1% (2/ 141)
Pegasys 360/ 180 jew 180 μg & Ribavirin 1000/ 1200 mg 72 jew 48 Ġimgħa (N = 942) Pażjenti b ’ VR f’ Ġimgħa 12 a (N = 876) 18% (157/ 876)
13.6%]
Pegasys 360/ 180 jew 180 μg & Ribavirin 1000/ 1200 mg 72 Ġimgħa (N = 473) SVR f’ Pażjenti b ’ VR f’ Ġimgħa 12 b (N = 100) 57% (57/ 100)
P=0.04
Pegasys 360/ 180 jew 180 μg & Ribavirin 1000/ 1200 mg 48 Ġimgħa (N = 469) SVR f’ Pażjenti b ’ VR f’ Ġimgħa 12 b (N = 57) 35% (20/ 57)
Low viral load
Viral load baxxa Viral load għolja Ġenotip 1/ 4
9% (21/ 245)
35% (56/ 159) 14% (97/ 686) 17% (140/ 846)
High viral load
Viral load baxxa Viral load għolja Ġenotip 2/ 3
10.3%]
35% (54/ 154) 13% (84/ 663) 58% (15/ 26)
11.5% [5.6%;
63% (22/ 35) 52% (30/ 58) (4/ 5)
17.4%]
37% (7/ 19) 35% (9/ 26) (3/ 10)
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL RVR = rapid viral response (HCV RNA undetectable) at week 4
Viral load baxxa Viral load għolja Stat ta ’ Ċirrosi
All treatment arms had 24 week treatment-free follow-up.
(2/ 5) (11/ 19) 8% (19/ 239)
Multiple regression and pooled group analyses evaluating the influence of treatment duration and use of induction dosing clearly identified treatment duration for 72 weeks as the primary driver for achieving a sustained virological response.
— (3/ 4)
Pegasys 360/ 180 or Pegasys 360/ 180 or 180 μ g 180 μ g & & Ribavirin 1000/ 1200 Ribavirin mg 1000/ 1200 mg 72 or 48 Weeks 72 Weeks (N = 942) (N = 473) Pts with SVR in Pts with VR at Wk 12 a VR at Wk 12 b (N = 876) (N = 100)
Ċirrosi
Pegasys 360/ 180 or 180 μ g & Ribavirin 1000/ 1200 mg 48 Weeks (N = 469) SVR in Pts with VR at Wk 12 b (N = 57)
22% (137/ 633)
Overall Low viral load High viral load Genotype 1/ 4 Low viral load High viral load Genotype 2/ 3 Low viral load High viral load Cirrhosis Status
(6/ 13)
18% (157/ 876) 57% (57/ 100) 35% (56/ 159) 63% (22/ 35) 14% (97/ 686) 54% (34/ 63) 17% (140/ 846) 55% (52/ 94) 35% (54/ 154) 63% (22/ 35) 13% (84/ 663) 52% (30/ 58) 58% (15/ 26) (4/ 5) (2/ 5) — (11/ 19) (3/ 4)
(3/ 6)
Ribavirin 1000/ 1200 mg 48 weeks Interferon Pegylated interferon Interferon plus ribavirin Pegylated interferon plus ribavirin
75 Tabella 13 Rispons Viroloġiku Sostenut f’ HALT- C skond il- Kors ta ’ Kura ta ’ Qabel fil - Popolazzjoni li ma Rrispondewx Pegasys 180 mcg & Ribavirin 1000/ 1200 mg 48 ġimgħa Kura ta ’ Qabel 27% (70/ 255) Interferon 34% (13/ 38) Pegylated interferon 13% (90/ 692) Interferon flimkien ma ’ ribavirin 11% (7/ 61) Pegylated interferon flimkien ma ’ ribavirin
75 HIV-HCV co-infected patients The virological responses of patients treated with Pegasys monotherapy and with Pegasys and ribavirin combination therapy in relation to genotype and pre-treatment viral load for HIV-HCV co- infected patients are summarised below in Table 14.
Pazjenti ko- infettati b’ HIV- HCV Ir- rispons viroloġiku ta ’ pazjenti kkurati b’ Pegasys waħdu u b’ terapija kombinata ta ’ Pegasys u ribavirin b’ relazzjoni mal- ġenotip u l- viral load ta ’ qabel il- kura għall- pazjenti ko- infettati b’ HIV- HCV huwa miġbur f’ Tabella 14 hawn isfel.
Odds Ratio (95% CI) = 2.89 (1.93 to 4.32), …. P-value (stratified Cochran-Mantel-Haenszel test) = < 0.0001 * Interferon alfa-2a 3MIU ribavirin 800 mg vs.
Pegasys 180μg, Odds Ratio (95% CI) = 2. 89 (1. 93 sa 4. 32), … Valur- p (test Cochran - Mantel- Haenzel stratifikat) = < 0. 0001 * Interferon alfa- 2a 3MIU ribavirin 800mg vs.
Peginterferon alfa-2a is found predominantly in the bloodstream and extracellular fluid as seen by the volume of distribution at steady-state (Vd) of 6 to 14 litres in humans after intravenous administration.
76 Peginterferon alfa- 2a jinstab prinċipalment fid- demm u fil- fluwidu extraċellulari kif jidher mill- volum ta ’ distribuzzjoni fi stat fiss (Vd) ta ’ 6 sa 14- il litru fil- bnedmin wara li jingħata minn ġol- vini.
After intravenous administration, the terminal half-life of peginterferon alfa-2a in healthy subjects is approximately 60 to 80 hours compared to values of 3-4 hours for standard interferon.
Wara għotja minn ġol- vini, l- half life terminali ta ’ peginterferon alfa- 2a f’ soġġetti b’ saħħithom hija ta ’ madwar 60 sa 80 siegħa meta imqabbel ma ’ valuri ta ’ 3 sa 4 siegħat għall- interferon normali.
76 Dose-proportional increases in exposure of Pegasys are seen in healthy subjects and in patients with chronic hepatitis B or C after once-weekly dosing.
Żidiet proporzjonati mad- doża f’ espożizzjoni għal Pegasys jidhru f’ soġġetti b’ saħħithom u f’ pazjenti b’ epatite B jew Ċ kronika wara dożaġġi ta ’ darba fil- ġimgħa.
Gender The pharmacokinetics of Pegasys after single subcutaneous injections were comparable between male and female healthy subjects.
Sess Il- karatteristiċi farmakokinetiċi ta ’ Pegasys wara injezzjoni waħda minn taħt il- ġilda kienu komparabbli bejn soġġetti maskili u femminili b’ saħħithom.
5.3 Preclinical safety data
77 5. 3 Studju qabel l- użu kliniku dwar is- sigurtà tal- mediċina
As with other alpha interferons, prolongation of the menstrual cycle was observed following administration of peginterferon alfa-2a to female monkeys.
Bħal fl- użu ta ’ alpha interferons oħrajn, kien osservat li ċ- ciklu menstruwali jitwal meta jingħata il- peginterferon alfa- 2a lil xadini ta ’ sess femminili.
Although no teratogenic effects were seen in the offspring delivered at term, adverse effects in humans cannot be excluded.
Għalkemm ma deher l- ebda effett teratoġeniku fiż- żgħar li twieldu fil- perijodu normali tat- tqala, ma jistgħux jiġu esklużi xi effetti avversi fil- bniedem.
sodium chloride polysorbate 80 benzyl alcohol (10 mg/ 1 ml) sodium acetate acetic acid water for injections
sodium chloride polysorbate 80 benzyl alcohol (10mg / 1ml) sodium acetate acetic acid ilma għall- injezzjonijiet
Keep the pre-filled syringe in the outer carton in order to protect from light.
Żomm il- kunjett fil- kartuna ta ’ barra sabiex tilqa ’ mid- dawl
0.5 ml of solution for injection in pre-filled syringe (siliconised Type I glass) with a plunger stopper and tip cap (butyl rubber laminated on the product facing side with fluororesin) with a needle.
0. 5 ml ta ’ soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest (Ħġieġ silikonizzat Tat- tip I) bi planġer stopper u b’ għatu tat- tarf (tal- gomma butyl, li minn naħħa li tmiss mal- prodott huwa laminat bil - flororeżin) b’ labra.
Available in packs of 1, 4 or 12.
Ipprovdut f’ pakketti ta ’ 1, 4 jew 12.
Any unused product or waste material should be disposed of in accordance with local requirements.
78 Kull fdal tal- prodott li ma jkunux intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Pegasys 180 micrograms solution for injection in pre-filled syringe
Pegasys 180 mikrogramma soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest
One pre-filled syringe contains peginterferon alfa-2a*.................................................................................... .180 micrograms Each syringe of 0.5 ml solution contains 180 micrograms peginterferon alfa-2a*.
Siringa waħda mimlija għal- lest fiha peginterferon alfa- 2a *............................................................................... 180 mikrogramma Kull siringa ta ’ 0. 5ml ta ’ soluzzjoni fiha 180 mikrogramma peginterferon alfa- 2a *.
80 4.2 Posology and method of administration
80 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Available data for patients infected with genotype 5 or 6 are limited; therefore combination treatment with 1000/ 1200 mg of ribavirin for 48 weeks is recommended.
Tagħrif disponibbli għal pazjenti infetti b’ ġenotip 5 jew 6 huwa limitat; għalhekk kura kombinatab’ 1000/ 1200 mg ta ’ ribavirin għal 48 ġimgħa hija rakkomandata.
81 Table 1:
81 Tabella 1.
*RVR = rapid viral response (HCV RNA undetectable) at week 4 and HCV RNA undetectable at week 24; **RVR = rapid viral response (HCV RNA negative) by week 4 LVL= ≤ 800,000 IU/ mL; HVL= > 800,000 IU/ mL
* RVR = Rispons virali mgħaġġel (HCV RNA mhix osservata) fir- raba ’ ġimgħa u HCV RNA mhix osservata f’ ġimgħa 24; ** RVR = rispons virali rapidu (negattiv għal HCV RNA) fir- raba ’ ġimgħa LVL= ≤800, 000 IU/ mL; HVL= > 800, 000 IU/ mL
82 Table 2:
82 Tabella 2.
Therapy should initially be re-instituted at 90 micrograms Pegasys and the neutrophil count monitored.
It- terapija għandha terġa ’ tinbeda b’ doża ta ’ 90 mikrogramma ta ’ Pegasys u l- livelli ta ’ newtrofili għandhom jiġu monitorati.
Specific recommendations for management of treatment-emergent anaemia are as follows: ribavirin should be reduced to 600 milligrams / day (200 milligrams in the morning and 400 milligrams in the evening) if either of the following apply:
Dawn li jmiss huma rakkomandazzjonijiet speċifiċi għall- immaniġġjar ta ’ anemija li tiżviluppa waqt il - kura: ribavirin għandu jitnaqqas għal 600 milligramma/ ġurnata (200 milligramma filgħodu u 400 milligramma filgħaxija) jekk xi waħda minn dawn li jmiss tapplika:
If the abnormality is reversed, ribavirin may be restarted at 600 milligrams daily, and further increased to 800 milligrams daily at the discretion of the treating physician.
83 600 milligramma kuljum, u tiġi miżjuda għal 800 milligramma kuljum skond id- diskrezzjoni tat- tabib responsabbli.
Dose Adjustment for Adverse Reaction (For further guidance see also text above)
Tranġar fid- Doża għal Reazzjonijiet Avversi (Għal aktar informazzjoni ara l- kitba ta ’ hawn fuq)
84 Patients with hepatic impairment In patients with compensated cirrhosis (eg, Child-Pugh A), Pegasys has been shown to be effective and safe.
84 jiġu monitorjati u għandu jkun hemm tnaqqis xieraq fid- doża ta ’ Pegasys matul it- terapija f’ każ ta ’ reazzjonijiet avversi.
* Grading according to Trey, Burns and Saunders (1966)
* Klassifikazzjoni skond Trey, Burns u Saunders (1966)
• Hypersensitivity to the active substance, to alpha interferons, or to any of the excipients • Autoimmune hepatitis • Severe hepatic dysfunction or decompensated cirrhosis of the liver • Neonates and young children up to 3 years old, because of the excipient benzyl alcohol (see section 4.4 for benzyl alcohol) • A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months (see section 4.4) • Initiation of Pegasys is contraindicated in HIV-HCV patients with cirrhosis and a Child-Pugh score ≥ 6
• Sensittività eċċessiva għas- sustanza attiva, għall- alfa interferons, jew għal xi sustanzi mhux attivi. • Epatite awtoimmuni • Disfunzjoni epatika severa jew ċirrożi dekompensata tal- fwied • Trabi u tfal żgħar taħt it- 3 snin, minħabba s- sustanża mhux attiva benzyl alcohol (ara sezzjoni 4. 4 għal benzyl alcohol) • Passat ta ’ mard sever tal- qalb eżistenti minn qabel, inkluż mard tal- qalb mhux stabbli jew mhux ikkontrollat fis- sitt xhur ta ’ qabel (ara sezzjoni 4. 4) • Bidu ta ’ Pegasys huwa kontra- indikat f’ pazjenti b’ HIV- HCV li għandhom ċirrożi u punteġġ Child- Pugh ta ’ ≥ 6.
85 4.4 Special warnings and precautions for use
85 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
If treatment with Pegasys is judged necessary in patients with existence or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and therapeutic management of the psychiatric condition.
Jekk kura b’ Pegasys hija meqjusa neċessarja f’ pazjenti b’ kondizzjonijiet psikjatriċi severi eżistenti jew fil- passat, din għandha tinbeda biss wara li jiġi żgurat immaniġġjar dijanjostiku u terapewtiku individwalizzat xieraq għall- kondizzjoni psikjatrika.
Haematological tests should be repeated after 2 and 4weeks and biochemical tests should be performed at 4weeks.
It- testijiet tad- demm għandhom jiġu ripetuti wara ġimagħtejn u 4 ġimgħat u testijiet bijokimiċi għandhom isiru wara 4 ġimgħat.
Progressive decreases after 8 weeks of therapy were infrequent.
Tnaqqis progressiv wara 8 ġimgħat ta ’ terapija kienu infrekwenti.
The decrease in ANC was reversible upon dose reduction or cessation of therapy (see section 4.2), reached normal values by 8 weeks in the majority of patients and returned to baseline in all patients after about 16 weeks.
It- tnaqqis fl- ANC kien riversibbli wara li tnaqqset id -- doża jew twaqqfet it- terapija (ara sezzjoni 4. 2), laħaq valuri normali wara 8 ġimgħat fil- maġġoranza tal- pazjenti u rritorna għall- linja bażi fil- pazjenti kollha wara madwar 16- il ġimgħa.
86 The occurrence of anaemia (haemoglobin < 10 g/ dl) has been observed in up to 15% of chronic hepatitis C patients in clinical trials on the combined treatment of Pegasys with ribavirin.
86 Il- preżenza ta ’ anemija (emoglobina < 10 g/ dl) ġiet osservata f’ mhux aktar minn 15% tal- pazjenti b’ epatite Ċ kronika fi provi kliniċi fuq il- kura kombinat ta ’ Pegasys ma ’ ribavirin.
Cardiovascular system Hypertension, supraventricular arrhythmias, congestive heart failure, chest pain and myocardial infarction have been associated with alpha interferon therapies, including Pegasys.
Sistema kardjovaskolari Pressjoni għolja, aritmija supraventrikolari, insuffiċjenza tal- qalb konġestiva, uġigħ fis- sider u infart mijokardijaku kienu assoċjati ma ’ terapiji b’ alpha interferons, inkluż Pegasys.
Patients with signs or symptoms compatible with autoimmune disorders should be evaluated carefully, and the benefit-risk of continued interferon therapy should be reassessed (see also Endocrine System in sections 4.4 and 4.8).
87 b’ sintomi kompatibbli ma ’ mard awtoimmuni għandhom jiġu evalwati bir- reqqa, u r- riskju- benefiċju li titkompla terapija b’ interferon għandu jerġa ’ jiġi evalwat (ara wkoll Sistema Endokrinarja f’ sezzjonijiet 4. 4 u 4. 8).
Pegasys must be used with caution in patients with psoriasis, and in cases of onset or worsening of psoriatic lesions, discontinuation of therapy should be considered.
Disturbi fil- ġilda L- użu ta ’ alpha interferons kien assoċċjat ma ’ tkabbir jew li kien il- kawża ta ’ psorjasi u sarkojodsi, u f’ każijiet ta ’ fejn ikun hemm bidu ta ’ jew aggravar ta ’ feriti psorjatiċi, it- twaqqif tat- terapija għandu jiġi kkunsidrat.
HIV/ HCV coinfection Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with Pegasys with or without ribavirin.
Infezzjoni fl- istess ħin b’ HIV- HCV Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkunu ser jittieħdu fl- istess ħin mat- terapija ta ’ HCV għall- għarfien u l- immaniġġjar ta ’ tossiċitajiet speċifiċi għal kull prodott u l- potenzjal għall- tossiċitajiet li jikkoinċidu ma ’ Pegasys waħdu jew ma ’ ribavirin.
Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy (HAART) may be at increased risk of developing lactic acidosis.
Pazjenti ko- infettati b’ HIV u li jkunu qed jirċievu Terapija Anti- Retrovirali Attiva Ħafna (HAART) jistgħu jkunu f’ riskju akbar li jiżviluppaw aċidożi lattika.
The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.5)
L- użu ta ’ ribavirin flimkien ma ’ zidovudine mhux rakkomandat minħabba żieda fir- riskju ta ’ anemija (ara sezzjoni 4. 5).
88 In patients co-infected with HIV-HCV, limited efficacy and safety data (N = 51) are available in subjects with CD4 counts less than 200 cells/ uL.
88 F’ pazjenti ko- infettati b’ HIV- HCV, tagħrif limitat dwar l- effikaċja u s- sigurtà (N = 51) huwa disponibbli f’ individwi b’ għadd ta ’ CD4 inqas minn 200 ċelluli/ uL.
In the same study, a 25% increase in the AUC of theophylline (marker of cytochrome P450 1A2 activity) was observed, demonstrating that Pegasys is an inhibitor of cytochrome P450 1A2 activity.
Fl- istess studju, żieda ta ’ 25% fl- AUC ta ’ theophylline (markatur ta ’ l- attivita ’ taċ- ċitokromju P450 1A2) kienet osservata, li turi li Pegasys huwa impeditur ta ’ l- attivita ’ taċ- ċitokroma P450 1A2.
Serum concentrations of theophylline should be monitored and appropriate dose adjustments of theophylline made for patients taking theophylline and Pegasys concomitantly.
Il - konċentrazzjonijiet fis- serum ta ’ theophylline għandhom ikunu monitorjati u tibdili xierqa fid- doża ta ’ theophylline għandhom isiru f’ pazjenti li qedgħin jieħdu t- theophylline u Pegasys flimkien.
Co-administration of ribavirin and didanosine is not recommended.
89 L- għotja flimkien ta ’ ribavirin u didanosine mhux rakkomandata.
89 Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated.
Kienet irrapp0rtata anemija li marret għall- agħar minħabba ribavirin meta zidovudine huwa parti mill - kors użat għall- kura ta ’ HIV għalkemm il- mekkaniżmu eżatt għad irid jinstab.
Ribavirin therapy is contraindicated in women who are pregnant.
Terapija b’ ribavirin hija kontra- indikata għal nisa waqt it - tqala.
Extreme care must be taken to avoid pregnancy in female patients or in partners of male patients taking Pegasys in combination with ribavirin.
Għandu jkun hemm attenzjoni kbira biex tiġi evitata tqala f’ pazjenti femminili jew u s- sieħeb ta ’ pazjenti maskili li qed jieħdu Pegasys f’ taħlita ma ’ r- ribavirin.
Female patients of childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
Pazjenti nisa li jistgħu joħorġu tqal u s- sieħba rġiel tagħhom għandhom jużaw kontraċettiv effettiv kull wieħed, waqt il- kura u għal 4 xhur wara li tintemm il- kura.
The frequency and severity of the most commonly reported adverse reactions with Pegasys are similar to those reported with interferon alfa-2a (see Table 4).
Il- frekwenza u s- severità tar- reazzjonijiet avversi li dehru l- aktar ta ’ spiss b' Pegasys huma simili ħafna għal dawk li dehru b’ interferon alfa- 2a( ara Tabella 4).
With the exception of pyrexia the frequency of the majority of the reported adverse reactions was notably less in CHB patients treated with Pegasys monotherapy compared with HCV patients treated with Pegasys monotherapy (see Table 4). Adverse events were experienced by 88% of Pegasys-treated patients as compared with 53% of patients in the lamivudine comparator group, while 6% of the Pegasys-treated and 4% of the lamivudine-treated patients experienced serious adverse events during the studies.
Bl- eċċezzjoni tad- deni, il- frekwenza tal - maġġoranza tar- reazzjonijiet avversi rrapportati kienet inqas sew f’ pazjenti b’ CHB li kienu ikkurati b’ monoterapija ta ’ Pegasys meta mqabbla ma ’ pazjenti b’ HCV kkurati b’ monoterapija ta ’ Pegasys (ara Tabella 4).
The percentage of patients with
Avvenimenti avversi dehru fi 88% tal- pazjenti kkurati b’ Pegasys meta mqabbel ma ’ 53% tal- pazjenti fil- grupp ta ’ paragun b’ lamivudine, filwaqt li 6% tal- pazjenti kkurati b’ Pegasys u 4% tal -
90 cirrhosis who withdrew from treatment was similar to that of the overall population in each treatment group.
Il- persentaġġ ta ’ pazjenti b’ ċirrożi li waqfu mill- kura kien simili għal dak tal- popolazzjoni globali f’ kull grupp ta ’ kura.
In HIV-HCV co-infected patients, the clinical adverse event profiles reported for Pegasys, alone or in combination with ribavirin, were similar to those observed in HCV mono-infected patients For HIV- HCV patients receiving Pegasys and ribavirin combination therapy other undesirable effects have been reported in ≥ 1% to ≤ 2% of patients: hyperlactacidaemia/ lactic acidosis, influenza, pneumonia, affect lability, apathy, tinnitus, pharyngolaryngeal pain, cheilitis, acquired lipodystrophy and chromaturia.
Għall- pazjenti b’ HIV- HCV li qed jirċievu terapija kombinata b’ Pegasys u ribavirin kienu rrappurtati effetti mhux mixtieqa oħra f’ ≥ 1% sa ≤ 2% tal- pazjenti: iperlattiċidemija/ aċidożi lattika, influwenza, pnewmonja, effett fuq il- lijabilità, apatija, tinnitus, uġigħ faringolarinġali, kelite, lipodistrofija miksuba u kromaturja.
91 Body system
91 Sistema tal - ġisem Neoplażmi beninni u malinni
Uncommon ≥ 1/ 1000 to < 1/ 100
Mhux komuni ≥ 1/ 1000 sa < 1/ 100 Neoplażma epatika
Immune system disorders
Disturbi tad - demm u tas - sistema limfatika
Sarcoidosis, thyroiditis
Disturbi fis - sistema immuni
, Idiopathic or thrombotic thrombocytopenic purpura
Purpura tromboċitopenika idjopatika jew trombotika
Optic neuropathy, papilledema, retinal vascular disorder, retinopathy, corneal ulcer
Newropatija ottika, Telf tal- vista papilledima, disturbi vaskulari fir - retina, retinopatija, ulċera tal- korneja
92 Body system
92 Sistema tal - ġisem
Investigations Injury and poisoning
93 Sistema tal - ġisem Korriment u avvelenament
Weight decreased
Komuni Ħafna ≥ 1/ 10
Substance overdose
Rari ≥ 1/ 10, 000 sa < 1/ 1000 Doża eċċessiva tas - sustanza
93 Post marketing adverse events
Avvenimenti avversi rrapportati wara t- tqegħid fis- suq
Treatment with Pegasys was associated with decreases in haematological values (leucopenia, neutropenia, lymphopenia, thrombocytopenia and haemoglobin), which generally improved with dose modification, and returned to pre-treatment levels within 4-8 weeks upon cessation of therapy (see sections 4.2 and 4.4).
Kura b' Pegasys kien assoċjata ma ’ tnaqqis fil- valuri ematoloġiċi( lewkopenja, newtropenja, limfopenja, tromboċitopenja u emoglobina), li ġeneralment marru għall- aħjar b’ tibdil tad- doża, u rrittornaw għall - livelli ta ’ qabel il- bidu tal- kura fi żmien 4- 8 ġimgħat wara li waqfet it- terapija (ara sezzjonijiet 4. 2 u 4. 4).
As with other interferons, a higher incidence of neutralising antibodies was seen in chronic hepatitis B.
Antikorpi anti- interferoni 1- 5% tal- pazjenti kkurati b' Pegasys żviluppaw antikorpi anti- interferon newtralizzanti Bħal b’ interferons oħra, dehret inċidenza ogħla ta ’ antikorpi newtralizzanti f’ epatite B kronika.
4.9 Overdose
94 4. 9 Doża eċċessiva
95 Table 5:
95 Tabella 5:
Predictability of response Please refer to section 4.2, in Table 2.
Tbassir tar- rispons Jekk jogħġbok ara sezzjoni 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata, f’ Tabella 2.
Dose-response in monotherapy In a direct comparison with 90 micrograms, the 180 micrograms-dose was associated with superior sustained virological response in patients with cirrhosis, but in a study in non-cirrhotic patients very similar results were obtained with doses of 135 micrograms and 180 micrograms.
Doża- Rispons skond id- doża fil- monoterapija F’ paragun dirett ma ’ 90 mikrogramma, id- doża ta ’ 180 mikrogramma kienet assoċjata ma ’ effett viroloġika sostenut superjuri f’ pazjenti biċ- ċirrożi, iżda fi studju b’ pazjenti mhux ċirrotiċi b’ dożi ta ’ 135 mikrogramma u 180 mikrogramma r- riżultati kienu simili ħafna.
Study NV15495 specifically recruited patients with a histological diagnosis of cirrhosis (about 80%) or transition to cirrhosis (about 20%).
L- istudju NV15495 speċifikament uża pazjenti b’ dijanjożi istoloġika ta ’ ċirrożi (bejn wieħed u ieħor 80%) jew transizzjonigħal ċirrożi (bejn wieħed u ieħor 20%).
These patients had stable HIV disease and mean CD4 T-cell count was about 500 cells/ µL.
Dawn il- pazjenti kellhom marda tal- HIV stabbli u l- għadd medju taċ- ċelloli T CD4 kien ta ’ madwar 500 ċellola/ µL. Għadhom għadejjin provi kliniċi f’ dawk li ma kellhomx rispons u f’ dawk li reġgħu rkadew.
For HCV monoinfected patients and HIV-HCV co-infected patients, for treatment regimens, duration of therapy and study outcome see Tables 6, 7, 8 and Table 14, respectively.
Rispons. viroloġiku kien iddefinit bħala
Virological response was defined as undetectable HCV RNA as measured by the COBAS AMPLICOR™ HCV Test, version 2.0 (limit of detection 100 copies/ ml equivalent to 50 International Units/ ml) and sustained response as one negative sample approximately 6 months after end of therapy.
96 livell ta ’ HCV RNA li ma jistax jitkejjel, kif imkejjel bit- test COBAS AMPLICOR™ HCV, verżjoni 2. 0 (limitu tal- kejl 100 kopja/ ml ekwivalenti għal 50 Kejl Internazzjonali/ ml) u rispons sostenut li deher bħala kampjun negattiv wieħed madwar 6 xhur wara t- tmiem tat- terapija.
NV15497 + NV15801
NV15497 +
Interferon alfa-2b
Interferon
(N=701)
(N=88)
(N=478)
(N=701)
Response
ġimgħa
Overall Sustained Response
Rispons sostenut komplessiv
The virological responses of HCV monoinfected patients treated with Pegasys monotherapy and with Pegasys and ribavirin combination therapy in relation to genotype and pre-treatment viral load and in relation to genotype, pre-treatment viral load and rapid virological response at week 4 are summarised in Table 7 and Table 8, respectively.
Ir- rispons viroloġiku ta ’ pazjenti infettati biss b’ HCV kkurati bil- monoterapija ta ’ Pegasys u bit- terapija kombinata ta ’ Pegasys u ribavirin b’ relazzjoni mal- ġenotip u l- viral load ta ’ qabel il- kura u b’ relazzjoni mal- ġenotip, l- viral load ta ’ qabel il- kura u r- rispons viroloġiku rapidu fir- raba ’ ġimgħa huma miġbura f’ Tabella 97 u f’ Tabella 8 rispettivament.
The results of study NV15942 provide the rationale for recommending treatment regimens based on genotype, baseline viral load and virological response at week 4 (see Tables 1, 7 and 8).
Ir- riżultati ta ’ l- istudju NV15942 jipprovdu r- raġunijiet wara l- għażla tat- tipi ta ’ kuri rakkomandati skond il- ġenotip, viral load fil- linja bażi u r- rispons viroloġiku fir- raba ’ ġimgħa (ara Tabelli 1, 7 u 8).
The difference between treatment regimens was in general not influenced by presence/ absence of cirrhosis; therefore treatment recommendations for genotype 1, 2 or 3 are independent of this baseline characteristic.
Id- differenza bejn it- tipi ta ’ kura ġeneralment ma kienetx influwenzata mill - preżenza/ assenza ta ’ ċirrożi; għalhekk il- kuri rakkomandata għall- ġenotip 1, 2 jew 3 hija indipendenti minn din il - karatteristika tal- linja bażi.
97 Table 7:
97 Tabella 7:
Genotype 1 Low viral load High viral load
Ġenotip 1
52% (142/ 271)* 65% (55/ 85) 47% (87/ 186)
(87/ 186)
80% (123/ 153) 77% (37/ 48) 82% (86/ 105) (9/ 11)
(123/ 153)
Table 8:
98 Tabella 8:
98 Although limited, data indicated that shortening treatment to 24 weeks might be associated with a higher risk of relapse (see Table 9).
Għalkemm limitat, it- tagħrif jindika li tqassir tal- kura għal 24 ġimgħa jista ’ jkun assoċjat ma ’ riskju akbar li wieħed jirkadi (ara Tabella 9).
Table 10:
99 Tabella 10.
99 The data indicated that shortening treatment to 16 weeks is associated with a higher risk of relapse (see Table 11).
Viral load baxxa = ≤ 800, 000 IU/ mL; Viral load għolja = > 800, 000 IU/ mL RVR = rispons virali rapidu (HCV RNA mhux osservat) fir- raba ’ ġimgħa It- tagħrif indika li tqassir tal- kura għal 16- il ġimgħa huwa assoċjat ma ’ riskju ogħla ta ’ rkadar (ara Tabella 11).
High viral load
Viral load baxxa Viral load għolja
(10/ 155)
6% (10/ 155) 20% (57/ 284)
10.3%]
1% (2/ 141) 9% (21/ 245)
11.5% [5.6%;
5% [0. 6%; 10. 3%] 11. 5% [5. 6%; 17. 4%]
(57/ 284)
P=0. 04 P=0. 0002
Superior efficacy of Pegasys compared to interferon alfa-2a was demonstrated also in terms of histological response, including patients with cirrhosis and/ or HIV-HCV co-infection.
Pazjenti b’ epatite Ċ kronika li ma rrispondewx għall- kura ta ’ qabel
100 Table 12:
100 Tabella 12:
Ribavirin 1000/ 1200 mg 48 weeks Interferon Pegylated interferon Interferon plus ribavirin Pegylated interferon plus ribavirin
101 Tabella 13 Rispons Viroloġiku Sostenut f’ HALT- C skond il- Kors ta ’ Kura ta ’ Qabel fil - Popolazzjoni li ma Rrispondewx Pegasys 180 mcg & Ribavirin 1000/ 1200 mg 48 ġimgħa Kura ta ’ Qabel 27% (70/ 255) Interferon 34% (13/ 38) Pegylated interferon 13% (90/ 692) Interferon flimkien ma ’ ribavirin 11% (7/ 61) Pegylated interferon flimkien ma ’ ribavirin
101 HIV-HCV co-infected patients The virological responses of patients treated with Pegasys monotherapy and with Pegasys and ribavirin combination therapy in relation to genotype and pre-treatment viral load for HIV-HCV co- infected patients are summarised below in Table 14.
Pazjenti ko- infettati b’ HIV- HCV Ir- rispons viroloġiku ta ’ pazjenti kkurati b’ Pegasys waħdu u b’ terapija kombinata ta ’ Pegasys u ribavirin b’ relazzjoni mal- ġenotip u l- viral load ta ’ qabel il- kura għall- pazjenti ko- infettati b’ HIV- HCV huwa miġbur f’ Tabella 14 hawn isfel.
HCV patients with normal ALT In study NR16071, HCV patients with normal ALT values were randomised to receive Pegasys 180 micrograms/ week and ribavirin 800 milligrams/ day for either 24 or 48 weeks followed by a 24 week treatment free follow-up period or no treatment for 72 weeks.
Pazjenti b’ HCV li għandhom b’ ALT normali Fl- istudju NR16071, pazjenti b’ HCV b’ valuri ta ’ ALT normali kienu randomised biex jirċievu Pegasys 180 mikrogramma/ ġimgħa u ribavirin 800 milligramma/ jum għal 24 jew 48 ġimgħa seġwit minn perijodu ta ’ wara ta ’ 24 ġimgħa mingħajr kura jew bla kura għal 72 ġimgħa.
Peginterferon alfa-2a is found predominantly in the bloodstream and extracellular fluid as seen by the volume of distribution at steady-state (Vd) of 6 to 14 litres in humans after intravenous administration.
102 Peginterferon alfa- 2a jinstab prinċpalment fid- demm u fil- fluwidu extraċellulari kif jidher mill- volum ta ’ distribuzzjoni fi stat fiss (Vd) ta ’ 6 sa 14- il litru fil- bnedmin wara li jingħata minn ġol- vini.
After intravenous administration, the terminal half-life of peginterferon alfa-2a in healthy subjects is approximately 60 to 80 hours compared to values of 3-4 hours for standard interferon.
Wara għotja minn ġol- vini, l- half life terminali ta ’ peginterferon alfa- 2a f’ soġġetti b’ saħħithom hija ta ’ madwar 60 sa 80 siegħa meta imqabbel ma ’ bejn 3 sa 4 siegħat għall- interferon normali.
The terminal half-life after subcutaneous administration in patients is longer with a mean value of 160 hours (84 to 353 hours).
Il- half life terminali hija itwal wara li jingħata minn taħt il- ġilda b’ valur medju ta ’ 160 (84 sa 353 siegħa).
The terminal half-life may not only reflect the elimination phase of the compound, but may also reflect the sustained absorption of Pegasys.
Il- half life terminali tista ’ ma tkunx qed tirrifletti biss il- fażi tal- eliminazzjoni tas- sustanza, iżda tista ’ tirrifletti ukoll l- assorbiment sostenut ta ’ Pegasys.
102 Dose-proportional increases in exposure of Pegasys are seen in healthy subjects and in patients with chronic hepatitis B or C after once-weekly dosing.
Żidiet proporzjonati mad- doża f’ espożizzjoni għal Pegasys jidhru f’ soġġetti b’ saħħithom u f’ pazjenti b’ epatite B jew Ċ kronika wara dożaġġi ta ’ darba fil- ġimgħa.
In chronic hepatitis B or C patients, peginterferon alfa-2a serum concentrations accumulate 2 to 3 fold after 6 to 8 weeks of once weekly dosing compared to single dose values.
F’ pazjenti b’ epatite B jew Ċ kronika, il- konċentrazzjonijiet ta ’ peginterferon alfa- 2a fis- serum jakkumulaw għal bejn darbtejn u 3 darbiet aktar wara 6 sa 8 ġimgħat ta ’ dożaġġ ta’ darba fil- ġimgħa meta imqabbel ma ’ figuri ta ’ doża waħda.
1295 ng·h / ml) but peak concentrations (9.1 vs.
1295 ng. h/ ml) iżda l- konċentrazzjonijiet massimi (9. 1 vs.
5.3 Preclinical safety data
103 5. 3 Studju qabel l- użu kliniku dwar is- sigurtà tal- mediċina
The major treatment-related change was reversible mild to moderate anaemia, the severity of which was greater than that produced by either active substance alone.
L- ikbar bidla relatata mal- kura kienet anemija riversibbli ħafifa jew moderata, u li s- severità tagħha kienet ogħla minn dik li sseħħ meta jingħataw xi wieħed mis- sustanzi attivi waħidhom.
Store in a refrigerator (2°C-8°C).
Aħżen fi friġġ (2°C – 8°C).
0.5 ml of solution for injection in pre-filled syringe (siliconised Type I glass) with a plunger stopper and tip cap (butyl rubber laminated on the product facing side with fluororesin) with a needle.
0. 5 ml ta ’ soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest (Ħġieġ silikonizzat tat- Tip I) bi planġer stopper u b’ għatu tat- tarf (tal- gomma butyl, li minn naħħa li tmiss mal- prodott huwa laminat bil - flororeżina) b’ labra.
Any unused product or waste material should be disposed of in accordance with local requirements.
104 Kull fdal tal- prodott li ma jkunux intużaw jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
105 ANNEX II
105 ANNESS II
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
MANIFATTUR( I) TAS- SUSTANZA BIJOLOĠIKA ATTIVA U DETENTUR( I) TA ’ L- AWTORIZZAZZJONI TAL - MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL - LOTT
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
MANIFATTUR( I) TAS- SUSTANZA BIJOLOĠIKA ATTIVA U DETENTUR( I) TA ’ L - AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- ĦRUĠ TAL - LOTT
340 Kingsland Street Nutley, New Jersey 07110 USA
340 Kingsland Street Nutley, New Jersey 07110 L- Istati Uniti
Roche Diagnostics GmbH Nonnenwald 2 D-82377 Penzberg Germany
Roche Diagnostics GmbH Nonnenwald 2 D- 82377 PenzbergiIl- Ġermanja
1 D-79639 Grenzach- Wyhlen Germany
1 D- 79639 Grenzach - Wyhlen Il- Ġermanja
The marketing authorisation holder should continue to submit yearly periodic safety update (PSUR) reports.
Id- Detentur ta ’ l- Awtorizazzjoni għat- tqegħid fis- Suq ser ikompli jagħti rapporti aġġornati perjodiċi dwar is- sigurtà (PSUR) kull sena.
107 ANNEX III
107 ANNESS III
109 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
109 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON – 1 x 135 μ g VIAL
PAKKETT TA ’ BARRA – KUNJETT 1 x 135 μg
Pegasys 135 micrograms solution for injection Peginterferon alfa-2a
Pegasys 135 mikrogramma f’ soluzzjoni għall- injezzjonijiet Peginterferon alfa- 2a
1 vial contains 135 micrograms of peginterferon alfa -2a.
Kunjett 1 fih 135 mikrogramma ta ’ peginterferon alfa- 2a
Also contains sodium chloride, polysorbate 80, benzyl alcohol (see the package leaflet for further information), sodium acetate, acetic acid and water for injections.
Fih ukoll sodium chloride, polisorbate 80, benzyl alcohol (għal aktar informazzjoni ara l- fuljett ta ’ tagħrif), sodium acetate, acetic acid u ilma għall- injezzjonijiet.
1 vial 135 micrograms in 1 ml
Kunjett 1 135 mikrogramma f’ 1 ml
Subcutaneous use Read the package leaflet before use
Użu għal taħt il- ġilda Aqra il- fuljett qabel l- użu
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom
Roche Registration Limited 6 Falcon Way Shire ParkWelwyn Garden City Hertfordshire AL7 1TW Ir- Renju Unit
111 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
111 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON – 4 x 135 μ g VIALS
PAKKETT TA ’ BARRA – 4 KUNJETTI x 135 μg
Pegasys 135 micrograms solution for injection Peginterferon alfa-2a
Pegasys 135 mikrogramma f’ soluzzjoni għall- injezzjoni Peginterferon alfa- 2a
1 vial contains 135 micrograms of peginterferon alfa-2a.
Kunjett 1 fih 135 mikrogramma ta ’ peginterferon alfa- 2a
Also contains sodium chloride, polysorbate 80, benzyl alcohol, (see the package leaflet for further information) sodium acetate, acetic acid and water for injections.
Fih ukoll sodium chloride, polisorbate 80, benzyl alcohol, (għal aktar informazzjoni ara l- fuljett ta ’ tagħrif), sodium acetate, acetic acid u ilma għall- injezzjonijiet.
4 vials 135 micrograms in 1 ml
4 kunjetti 135 mikrogramma f’ 1 ml
113 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
113 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI IŻ- ŻGĦAR EWLENIN
SINGLE DOSE 135 μ g VIAL
KUNJETT TA ’ DOŻA WAĦDA B’ 135 μg
Pegasys 135 micrograms solution for injection SC use
Pegasys 135 mikrogramma f’ soluzzjoni għall- injezzjoni Użu għal taħt il- ġilda
135 μ g in 1 ml
135 μg f’ 1 ml
114 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
114 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON – 1 x 180 μ g VIAL
PAKKETT TA ’ BARRA – KUNJETT 1 x 180 μg
Pegasys 180 micrograms solution for injection Peginterferon alfa-2a
Pegasys 180 mikrogramma f’ soluzzjoni għall- injezzjoni Peginterferon alfa- 2a
STATEMENT OF ACTIVE SUBSTANCE(S)
UŻU TAS- SUSTANZA( I) ATTIVA
1 vial contains 180 micrograms of peginterferon alfa-2a.
Kunjett 1 fih 180 mikrogramma ta ’ peginterferon alfa- 2a
1 vial 180 micrograms in 1 ml
Kunjett 1 180 mikrogramma f’ 1 ml
SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE
PREKAWZJONIJIET SPEĊJALI GĦAR - RIMI TA ’ PRODOTTI MEDIĊINALI
116 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
116 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON – 4 x 180 μ g VIALS
PAKKETT TA ’ BARRA – 4 KUNJETTI x 180 μg
4 vials 180 micrograms in 1 ml
4 kunjetti 180 mikrogramma f’ 1 ml
118 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
118 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI IŻ- ŻGĦAR EWLENIN
SINGLE DOSE 180 μ g VIAL
KUNJETT B’ 180 μg TA ’ DOŻA WAĦDA
Pegasys 180 micrograms solution for injection SC use
Pegasys 180 mikrogramma f’ soluzzjoni għall- injezzjoni Użu għal taħt il- ġilda
180 μ g in 1 ml
180 μg f’ 1 ml
119 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
119 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON – 1 x 135 μ g PRE-FILLED SYRINGE
PAKKETT TA ’ BARRA – 1 x 135 μg SIRINGA MIMLIJA GĦAL- LEST
Pegasys 135 micrograms solution for injection in pre-filled syringe Peginterferon alfa-2a
Pegasys 135 mikrogramma f’ soluzzjoni għall- injezzjoni ġo siringa mimlija għallest Peginterferon alfa- 2a
1 pre-filled syringe contains 135 micrograms of peginterferon alfa – 2a.
Siringa mimlija għal lesta 1 fiha 135 mikrogramma ta ’ peginterferon alfa- 2a
1 pre-filled syringe + 1 injection needle 135 micrograms in 0.5 ml
Siringa mimlija għal- lest 1 + labra 1 għall- injezzjoni 135 mikrogramma f’ 0. 5 ml
Store in a refrigerator Do not freeze Keep the pre-filled syringe in the outer carton in order to protect from light
Aħżen fi friġġ Tagħmlux fil- friża Żomm is- siringa mimlija għal lest fil- kartuna ta ’ barra sabiex tilqa ’ mid- dawl
121 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
121 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
OUTER CARTON – 4 x 135 μ g PRE-FILLED SYRINGES
PAKKETT TA ’ BARRA – 4 SIRINGI MIMLIJIN GĦAL- LEST x 135 μg
Pegasys 135 micrograms solution for injection in pre-filled syringe Peginterferon alfa-2a
Pegasys 135 mikrogramma f’ soluzzjoni għall- injezzjoni ġo siringa mimlija għal- lest Peginterferon alfa- 2a