qanastek/EMEA-V3 huggingface dataset:
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.
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.
Adverse events or laboratory abnormalities led to 5% of patients withdrawing from Pegasys treatment, while less than 1% of patients withdrew from lamivudine treatment for these reasons.
Avvenimenti avversi jew anormalitajiet tal- laboratorju wassal 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.
The percentage of patients with
Il- persentaġġ ta ’ pazjenti b’ ċirrożi li waqfu mill- kura kien simili għal dak tal- popolazzjoni globali f’ kull grupp ta ’ kura.
38 cirrhosis who withdrew from treatment was similar to that of the overall population in each treatment group.
38 Epatite Ċ kronika f’ pazjenti li ma rrispondewx qabel
In a clinical trial of non-responder patients to prior pegylated interferon alfa-2b/ ribavirin, which exposed patients to either 48 or 72 weeks of treatment, the frequency of withdrawal for adverse events or laboratory abnormalities from Pegasys treatment and ribavirin treatment was 6% and 7%, respectively, in the 48 week arms and 12% and 13%, respectively, in the 72 week arms.
Fi prova klinika ta ’ pazjenti li ma rrispondewx għal pegylated interferon alfa- 2b/ ribavirin mogħti qabel, li esponiet il- pazjenti għal 48 jew 72 ġimgħa ta ’ kura, il- frekwenza ta ’ waqfien minħabba avvenimenti avversi jew anormalitajiet tal - laboratorju kkawżati minn kura ta ’ Pegasys u kura ta ’ ribavirin kienet 6% u 7% rispettivament, fil - gruppi ta ’ 48 ġimgħa u 12% u 13% rispettivament, fil- gruppi ta ’ 72 ġimgħa.
Limited safety data (N= 51) are available in co- infected patients with CD4+ cell counts < 200/ µl.
Tagħrif limitat dwar is- sigurtà (N= 31) huwa disponibbli f’ pazjenti ko- infettati b’ għadd ta ’ ċelloli ta ’ CD4+ < 200/ µl.
Upper respiratory infection, bronchitis, oral candidiasis, herpes simplex, fungal, viral and bacterial infections
Neoplażma epatika
Pneumonia, skin infection
Disturbi tad - demm u tas - sistema limfatika
Endocarditis, otitis externa
Tromboċitopenja, anemija, limfo - adenopatija
Neoplasms benign and malignant
Panċitopenja
Hepatic neoplasm
Anemija aplastika
39 Body system
39 Sistema tal - ġisem Disturbi fis - sistema immuni
Uncommon ≥ 1/ 1000 to < 1/ 100
Mhux komuni ≥ 1/ 1000 sa < 1/ 100 Sarkojdożi, tirojdite
Rare ≥ 1/ 10,000 to < 1/ 1000
Rari ≥ 1/ 10, 000 sa < 1/ 1000 Anafilassi, lupus erythematosus sistemika,, artrite rewmatojda
Very rare < 1/ 10,000
Rari ħafna < 1/ 10, 000 Purpura tromboċitopenika idjopatika jew trombotika
Sarcoidosis, thyroiditis
Disturbi fis - sistema endokrinarja
Metabolism and Nutrition Disorders
Disturbi fil - metaboliżmu u n- nutrizzjoni
Dehydration
Deidratazzjoni
Optic neuropathy, papilloedema, retinal vascular disorder, retinopathy, corneal ulcer
Newropatija ottika, Telf tal- vista papilledima, disturbi vaskulari fir- retina, retinopatija, ulċera tal- korneja
Tachycardia, palpitations, oedema peripheral
Takikardja, palpitazzjonijiet, edima periferali
Myocardial infarction, congestive heart failure, angina, supraventricular tachycardia, arrhythmia, atrial fibrillation, pericarditis, cardiomyopathy
Infart mijokardijaku, insuffiċjenza tal- qalb konġestiva, anġina, takikardja supraventrikolari, arritmija, fibrillazzjoni atrijali, perikardite, kardjomijopatija
40 Body system
40 Sistema tal - ġisem
Uncommon ≥ 1/ 1000 to < 1/ 100
Mhux komuni ≥ 1/ 1000 sa < 1/ 100
Alopecia, dermatitis,
Alopeċja, dermatite, ħakk, ġilda xotta
Rash, sweating increased,
Raxx, żieda fl - għaraq, psorjasi, urtikarja, ekżema, disturbi fil- ġilda, reazzjoni ta ’ fotosensittività, tgħereq ħafna matul il- lejl
Toxic epidermal necrolysis,
Nekrolisi epidermali tossika, Sindrome Stevens - Johnson, anġjoedima, eritema multiforme
tissue disorders
Disturbi muskolu - skeletrali, tal - connective tissue u ta ’ l- għadam
pruritis, dry skin
Mijalġja, artralġja
psoriasis, urticaria, eczema, skin disorder, photosensitivity reaction, night sweats
Uġigħ fid- dahar, artrite, indebboliment tal- muskoli, uġigħ fl- għadam, uġigħ fl- għonq, uġigħ muskolu - skeletrali, bugħawwieġ fil - muskoli
Stevens-Johnson syndrome, angioedema, erythema multiforme
Majosite
Musculoskeletal Myalgia, connective tissue arthralgia and bone disorders
Disturbi fil - kliewi u fis - sistema urinarja
Myositis
Insuffiċjenza tal - kliewi
Renal insufficiency
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata
General disorders Pyrexia, and rigors*, administration pain*, site conditions asthenia, fatigue, injection site reaction*, irritability*
Deni, rogħda *, uġigħ *, astenja, għeja, reazzjoni fis- sit ta ’ l - injezzjoni *, irritabilità *
41 Post marketing adverse events
Avvenimenti avversi rrapportati wara t- tqegħid fis- suq
Eye Disorders:
41 Disturbi fl- għajnejn:
ALT increase, bilirubin increase, electrolyte disturbance (hypokalaemia, hypocalcaemia, hypophosphataemia), hyperglycaemia, hypoglycaemia and elevated triglycerides (see section 4.4.).
Valuri tal- laboratorju Kura b' Pegasys kien assoċċjat ma ’ valuri tal- laboratorju anormali: żieda fl- ALT, żieda fil- bilirubin, disturb fil- livelli ta ’ l- elektroliti (ipokalimija, ipokalċimija, ipofosfatimija), ipergliċemija, ipogliċemija u livelli għoljin ta ’ trigliċeridi (ara sezzjoni 4. 4).
With both Pegasys monotherapy, and also the combined treatment with ribavirin, up to 2% of patients experienced increased ALT levels that led to dose modification or discontinuation of the treatment.
Kemm fil- monoterapija b' Pegasys, kif ukoll fit- terapija kombinata ma ’ ribavirin, sa 2% mill- pazjenti kellhom żieda fil- livelli tal- ALT li wasslet għal modifikazzjoni fid- doża jew għall- twaqqif tal- kura.
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 kienet 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).
Anti-interferon antibodies 1-5% of patients treated with Pegasys developed neutralising anti-interferon antibodies.
Antikorpi anti- interferon 1- 5% tal- pazjenti kkurati b' Pegasys żviluppaw antikorpi anti- interferon newtralizzanti.
As with other interferons, a higher incidence of neutralising antibodies was seen in chronic hepatitis B.
Bħal b’ interferons oħra, dehret inċidenza ogħla ta ’ antikorpi newtralizzanti f’ epatite B kronika.
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.
Thyroid function Pegasys treatment was associated with clinically significant abnormalities in thyroid laboratory values requiring clinical intervention (see section 4.4).
Funzjoni tat- tirojde Kura b' Pegasys kien assoċjat ma ’ anormalitajiet ta ’ sinifikanza klinika fir- riżultati tal- figuri tal - laboratorju tat- tirojde li kellhom bżonn intervent kliniku (ara sezzjoni 4. 4).
The frequencies observed (4.9%) in patients receiving Pegasys/ ribavirin (NV15801) are similar to those observed with other interferons.
Il- frekwenzi osservati (4. 9%) f’ pazjenti li rċevew Pegasys/ ribavirin (NV15801) huma simili għal dawk osservati b’ interferons oħrajn.
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.
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.
Decrease in platelets below 50,000/ mm3 was observed in 10% and 8% of patients receiving Pegasys monotherapy and combination therapy, respectively.
Tnaqqis fil- plejtlits taħt 50, 000/ mm3 kien osservat f’ 10% u 8% tal- pazjenti li rċevew Pegasys waħdu jew f’ terapija kombinata, rispettivament.
Overdoses involving between two injections on consecutive days (instead of weekly interval) up to daily injections for 1 week (ie, 1260 micrograms/ week) have been reported.
Dożi eċċessivi li jvarjaw minn żewġ injezzjonijiet fi ġranet konsekuttivi (minflok interval ta ’ ġimgħa) sa injezzjonijiet kuljum għal ġimgħa waħda (jiġifieri, 1260 mikrogramma/ ġimgħa) kienu rapportati.
None of these patients experienced unusual, serious or treatment-limiting events.
L - ebda minn dawn il- pazjenti ma esperjenzaw sintomi mhux tas- soltu, serji jew li jillimitaw il- kura.
Weekly doses of up to 540 and 630 micrograms have been administered in renal cell carcinoma and chronic myelogenous leukaemia clinical trials, respectively.
Dożi sa 540 u 630 mikrogramma fil- ġimgħa kienu mogħtija fi provi kliniċi f’ każijiet ta ’ karċinoma taċ- ċelloli renali u b’ lewkimja majeloġenika kronika, rispettivament.
Dose limiting toxicities were fatigue, elevated liver enzymes, neutropenia and thrombocytopenia, consistent with interferon therapy.
Tossiċitajiet li llimitaw id- doża kienu għejja, livelli ta ’ enżimi tal- fwied għolja, newtropenja u tromboċitopenja, konsistenti ma ’ terapija b’ interferon.
The conjugation of PEG reagent (bis-monomethoxypolyethylene glycol) to interferon alfa-2a forms a pegylated interferon alfa-2a (Pegasys).
Il- konjugazzjoni tar- reaġent PEG (bis- monometossi- poli- etilin glikol) ma ’ interferon alfa- 2a jifforma pegylated interferon alfa- 2a (Pegasys).
Interferon alfa-2a is conjugated with bis-[monomethoxy polyethylene glycol] at a degree of substitution of one mole of polymer/ mole of protein.
Interferon alfa- 2a huwa kkonjugat ma ’ bis - [monomethoxy polyethylene glycol] fi grad ta ’ sostituzzjoni ta ’ mole waħda ta ’ polymer/ mole ta ’ proteina.
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.
HCV RNA levels decline in a biphasic manner in responding patients with hepatitis C who have received treatment with 180 micrograms Pegasys.
Il- livelli ta ’ HCV RNA jonqsu b’ mod bi- fażiku f’ pazjenti b’ epatite Ċ li rrispondew għall- kura b’ 180 mikrogramma Pegasys.
The first phase of decline occurs 24 to 36 hours after the first dose of Pegasys and is followed by 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.
In study WV16241, the primary efficacy endpoints were ALT normalisation and HBV-DNA below 2 x 104 copies/ ml.
Fl- istudju WV16241, il- miri primarji tal- effikaċja kienu normalizzazzjoni ta ’ ALT u HBV DNA taħt 2 x 104 kopja/ ml.
43 Table 5:
43 Tabella 5:
Histological response was similar across the three treatment groups in each study; however, patients showing a sustained response 24 weeks after the end of treatment were significantly more likely to also show histological improvement.
Ir- rispons istoloġiku kien simili tul it- tlett gruppi ta ’ kura f’ kull studju; madanakollu, pazjenti li wrew rispons sostenut 24 ġimgħa wara t- tmiem tal- kura kienu sinifikatament aktar probabbli li juru wkoll titjib istoloġiku.
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.
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.
Confirmatory clinical trials in treatment-naïve patients All clinical trials recruited interferon-naïve patients with chronic hepatitis C confirmed by detectable levels of serum HCV RNA, elevated levels of ALT (with the exception of study NR16071) and a liver biopsy consistent with chronic hepatitis.
Provi kliniċi konfermatorji f’ pazjenti li qatt ma jkunu ħadu kura qabel Il- provi kliniċi kollha użaw pazjenti interferon- naive li kellhom epatite Ċ kronika kkonfermata mill - livelli mkejla fis- serum ta ’ HCV RNA, livelli elevati ta ’ ALT (bl- eċċezzjoni ta ’ studju NR16071) u minn bijopsija tal- fwied konsistenti ma ’ epatite kronika.
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 transizzjoni għal 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.
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.
Għadhom għadejjin provi kliniċi f’ dawk li ma kellhomx rispons u f’ dawk li rkadew.
Virological response was defined as undetectable HCV RNA as measured by the COBAS AMPLICOR™ HCV Test, version 2.0
Rispons viroloġika kien iddefinit bħala
44 (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.
44 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.
Virological Response in HCV Patients
Rispons Viroloġika f’ Pazjenti b’ HCV
Study NV15495 Study
Studju NV15495 Studj
NV15497 + NV 15801
NV15497 +
NV15942
NV15942 Pegasys
Pegasys 180 mcg
180 mcg
Interferon Pegasys Interferon Pegasys Pegasys alfa-2a 180 mcg alfa-2a 180 mcg 180 mcg
180 mcg
Interferon alfa-2b
alfa- 2a 3 MIU
6 MIU/
180 mcg
3 MIU 3 MIU & & &
alfa- 2b 3 MIU
Ribavirin Ribavirin 1000/ 1200 1000/ 1200 mg mg
1000/ 1200
Ribavirin 1000/ 1200 mg
1000/ 1200
(N=701)
1000/ 1200
(N=478)
(N=88)
(N=87)
(N=701)
(N=88)
(N=87)
weeks 48 weeks 48
48
at End of Treatment
ġimgħa
Sustained Response
Risponssost enut ġenerali
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, 7and 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).
45 Table 7:
45 Tabella 7:
Pegasys Pegasys Pegasys Pegasys Pegasys 180 mcg 180 mcg 180 mcg 180 mcg 180 mcg
Pegasys Pegasys Pegasys Pegasys
Interferon alfa-2b 3 MIU
180 mcg 180 mcg 180 mcg 180 mcg
&
u u u u
Ribavirin Ribavirin Ribavirin Ribavirin Ribavirin
u
800 mg
Ribavirin
1000/ 1200 mg 800 mg 1000/ 1200 mg 1000/ 1200 mg
1000/ 1200
48 weeks 48 weeks 48 weeks
48 ġimgħa 48 ġimgħa
46 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 9:
46 Tabella 9:
The sustained viral response achieved with 16 weeks of treatment and with 24 weeks of treatment was also examined in a retrospective subgroup analysis of patients who were HCV RNA negative by week 4 and had a LVL at baseline (see Table 10)
Ir- rispons virali sostenut miksub b’ 16- il ġimgħa ta ’ kura u b’ 24 ġimgħa ta ’ kura kien eżaminat ukoll f’ analiżi retrospettiv ta ’ sottogrupp ta ’ pazjenti li kienu negattivi għal HCV RNA mar- raba ’ ġimgħa u li kellhom LVL fil- linja bażi (ara Tabella 10).
Sustained Virological Response Overall and Based on Rapid Viral Response by Week4 for Genotype 2 or 3 after Pegasys Combination Therapy with Ribavirin in HCV Patients Study NV17317
Rispons Viroloġiku Sostenut Totali u Bbażat fuq Rispons Virali Rapidu mar- Raba ’ Ġimgħa għall- Ġenotip 2 jew 3 wara Terapija Kombinata ta ’ Pegasys b’ Ribavirin f’ Pazjenti b’ HCV
Treatment difference 95%CI
95% CI
Ribavirin 800 mg 16 weeks
Ribavirin 800 mg
Ribavirin 800 mg 24 weeks
Ribavirin 800 mg 24 ġimgħa
Genotype 2 or 3
16- il ġimgħa - 10. 6% [- 15. 5%; - 0. 06%] Ġenotip 2 jew 3
-10.6%
- 8. 2% [- 12. 8%; - 3. 7%]
Genotype 2 or 3 RVR
Ġenotip 2 jew 3 RVR
82% (378/ 461)
82% (378/ 461) 90%
(147/ 166)
89% (147/ 166) 94%
-9.7% [-15.9%; -
- 9. 7% [- 15. 9%; - 3. 6%]
88%
P=0. 11
3.6%]
Viral load għolja
(231/ 295)
78% (231/ 295) 88%
47 The data indicated that shortening treatment to 16 weeks is associated with a higher risk of relapse (see Table 11).
47 It- tagħrif indika li tqassir tal- kura għal 16- il ġimgħa huwa assoċjat ma ’ riskju ogħla ta ’ rkadar (ara Tabella 11).
difference 95%CI
& Ribavirin 800 mg 24 ġimgħa
Ribavirin 800 mg 16 weeks
95% CI
Ribavirin 800 mg 24 weeks
Ribavirin 800 mg 16- il ġimgħa Ġenotip 2 jew 3 RVR
9.3% [5.2%;
9. 3% [5. 2%; 13. 6%]
13.6%]
P < 0. 0001
Low viral load
Viral load baxxa
6%
6% (10/ 155)
9% (21/ 245)
1% (2/ 141)
5% [0.6%;
5% [0. 6%; 10. 3%]
P=0.0002
P=0. 04
High viral load
Viral load għolja
10.3%]
20% (57/ 284)
20%
9% (21/ 245)
11.5% [5.6%;
11. 5% [5. 6%; 17. 4%]
(57/ 284)
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.
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.
Chronic hepatitis C prior treatment non-responder patients In study MV17150, patients who were non-responders to previous therapy with pegylated interferon alfa-2b plus ribavirin were randomized to four different treatments: • Pegasys 360 mcg/ week for 12 weeks, followed by 180 mcg/ week for a further 60 weeks • Pegasys 360 mcg/ week for 12 weeks, followed by 180 mcg/ week for a further 36 weeks • Pegasys 180 mcg/ week for 72 weeks • Pegasys 180 mcg/ week for 48 weeks All patients received ribavirin (1000 or 1200 mg/ day) in combination with Pegasys.
Fl- istudju MV17150, pazjenti li ma kienux irrispondew għall- terapija ta ’ qabel b’ pegylated interferon alfa- 2b flimkien ma ’ ribavirin kienu randomised għall erba ’ kuri differenti: • Pegasys 360 mcg/ ġimgħa għal 12- il ġimgħa, segwit minn 180 mcg/ ġimgħa għal 60 ġimgħa oħra • Pegasys 360 mcg/ kull ġimgħa għal 12- il ġimgħa, segwit minn 180 mcg/ week għal 36 ġimgħa oħra • Pegasys 180 mcg/ ġimgħa għal 72 ġimgħa • Pegasys 180 mcg/ ġimgħa għal 48 ġimgħa Il- pazjenti kollha rċevew ribavirin (1000 jew 1200 mg/ kuljum) flimkien ma ’ Pegasys.
All treatment arms had 24 week treatment-free follow-up.
Il- gruppi ta ’ kura kollha kellhom perijodu ta ’ wara ta ’ 24 ġimgħa bla kura.
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.
Analiżi ta ’ regressjoni multipla u analiżi miġbura ta ’ grupp li vvalutaw l- influwenza tat- tul ta ’ kura u l - użu ta ’ dożaġġ ta ’ induzzjoni identifikaw b’ mod ċar tul ta ’ kura ta ’ 72 ġimgħa bħala l- induttur prinċipali biex jintlaħaq rispons viroloġiku sostenut.
Differences in sustained virological response (SVR) based on treatment duration, demographics and best responses to previous treatment are displayed in Table 12.
Differenzi fir- rispons viroloġiku sostenut ibbażati fuq it- tul u d- demografiċi tal- kura huma mniżżla f’ Tabella 12.
48 Table 12:
48 Tabella 12:
Week 12 Virological Response (VR) and Sustained Virological Response (SVR) in Patients with Virological Response at Week 12 after Treatment with Pegasys and Ribavirin Combination Therapy in Nonresponders to Peginterferon alfa-2b plus Ribavirin.
Globali
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)
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)
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)
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)
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
Viral load baxxa Viral load għolja Ġenotip 1/ 4
Cirrhosis Noncirrhosis Best Response during Previous Treatment
Viral load baxxa Viral load għolja Stat ta ’ Ċirrosi
Ribavirin 1000/ 1200 mg 48 weeks Interferon Pegylated interferon Interferon plus ribavirin Pegylated interferon plus ribavirin
49 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
49 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.
Ribavirin 800 mg
Ribavirin 800 mg
48 weeks 48 weeks
48 ġimgħa 48 ġimgħa
The absorption of Pegasys is sustained with peak serum concentrations reached 72 to 96 hours after dosing.
L- assorbiment ta ’ Pegasys huwa sostenut, bil- konċentrazzjoni massima fis- serum tintlħaq bejn 72 u 96 il- siegħa wara li tingħata d- doża.
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.
50 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.
From mass balance, tissue distribution and whole body autoradioluminography studies performed in rats, peginterferon alfa-2a is distributed to the liver, kidney and bone marrow in addition to being highly concentrated in the blood.
Minn analiżi tal- bilanċi tal- piż, distribuzzjoni fit- tessuti u awtoradjuluminografija tal- ġisem kollu li saru fil- far, peginterferon alfa- 2a jinfirex fil- fwied, kliewi u fil- mudullun tal- għadam minbarra li huwa kkonċentrat ħafna fid- demm.
The metabolism of Pegasys is not fully characterised; however studies in rats indicate that the kidney is a major organ for excretion of radiolabelled material.
Il- metaboliżmu ta ’ Pegasys m’ huwiex karatterizzat kompletament; iżda studji li saru fil- far jindikaw li l - kilwa hija organu prinċipali involut fit- tneħħija ta ’ materjal radjutikkettat.
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, il- 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.
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 ta ’ l- eliminazzjoni tas- sustanza, iżda tista ’ tirrifletti ukoll l- assorbiment sostenut ta ’ Pegasys.
50 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 darbtejn u 3 darbiet aktar wara 6 sa 8 ġimgħat ta ’ dożaġġ ta’ darba fil- ġimgħa meta imqabbel ma ’ figuri ta ’ doża waħda.
There is no further accumulation after 8 weeks of once weekly dosing.
M’ hemmx aktar akkumulazzjoni wara 8 ġimgħat ta ’ dożaġġ ta ’ darba fil- ġimgħa.
The peak to trough ratio after 48 weeks of treatment is about 1.5 to 2.
Il- proporzjon bejn il- massimu u l- minimu wara 48 il- ġimgħa ta ’ kura huwa ta ’ madwar 1. 5 sa 2.
Peginterferon alfa-2a serum concentrations are sustained throughout one full week (168 hours).
Il- konċentrazzjonijiet fis- serum ta ’ Peginterferon alfa- 2a huma sostenuti għal ġimgħa sħiħa (168 siegħa).
In patients with end stage renal disease undergoing haemodialysis, there is a 25% to 45% reduction in the clearance, and doses of 135 micrograms result in similar exposure as 180 micrograms doses in patients with normal renal function (see section 4.2).
F’ pazjenti b’ mard renali ta ’ l- aħħar stadju li jkunu qed jagħmlu dijalisi tad- demm, hemm tnaqqis ta ’ bejn 25% sa 45% fit- tneħħijja, u dożi ta ’ 135 mikrogramma jirriżultaw f’ espożizzjoni simili għal dawk b’ dożi ta ’ 180 mikrogramma f’ pazjenti b’ funzjoni renali normali (ara sezzjoni 4. 2).
Based on drug exposure, pharmacodynamic response and tolerability, a lower dose of Pegasys is not needed in the geriatric patient (see 4.2).
M’ hemmx bżonn ta ’ tnaqqis fid- doża ta ’ Pegasys għall- pazjenti ġerjatriċi, meta jiġu ikkunsidrati l- esponimenti għas - sustanza, ir- rispons farmakodinamiku u t- tolerabilità (ara sezzjoni 4. 2).
Hepatic impairment The pharmacokinetics of Pegasys were similar between healthy subjects and patients with hepatitis B or C.
Insuffiċjenza Epatika Il- farmakokinetika ta ’ Pegasys f’ individwi b’ saħħithom u f’ pazjenti b ’ epatite B jew Ċ kienet simili.
Comparable exposure and pharmacokinetic profiles were seen in cirrhotic (Child-Pugh Grade A) and non-cirrhotic patients.
Kien hemm espożizzjoni u profili farmakokinetiċi komparabli f’ pazjenti b’ ċirrożi (Child- Pugh ta ’ Grad A) u f’ pazjenti mingħajr ċirrożi.
Site of administration Subcutaneous administration of Pegasys should be limited to the abdomen and thigh, as the extent of absorption based on AUC was about 20% to 30% higher upon injection in the abdomen and thigh.
Mnejn jingħata L- għotja minn taħt il- ġilda ta ’ Pegasys għandha tiġi limitata għall- addome u l- koxxa, minħabba li l- grad ta ’ assorbiment li deher mill- AUC kien bejn 20% sa 30% ogħla wara injezzjoni fl- addome u fil- koxxa.
Exposure to Pegasys was decreased in studies following administration of Pegasys in the arm compared to administration in the abdomen and thigh.
Kien hemm tnaqqis fl- espożizzjoni għal Pegasys meta ingħata fid- dirgħajn meta mqabbel ma ’ għotja fl - addome u fil- koxxa.
5.3 Preclinical safety data
51 5. 3 Studju qabel l- użu kliniku dwar is- sigurtà tal- mediċina
The Non-clinical toxicity studies conducted with Pegasys were limited due to species specificity of interferons.
L- istudji mhux kliniċi ta ’ tossiċità li saru b' Pegasys huma limitati minħabba l- ispeċifiċitá ta ’ l - interferons fl- ispeċi.
Acute and chronic toxicity studies have been carried out in cynomolgus monkeys, and the findings observed in peginterferon dosed animals were similar in nature to those produced by interferon alfa-2a.
Saru studji fuq it- tossiċità akuta u kronika fix- xadini cynomolgus, u ir- riżultati osservati fl- annimali li ngħatalhom peginterferon kienu simili għal dawk prodotti minn interferon alfa - 2a.
Reproductive toxicity studies have not been performed with Pegasys.
Ma sarux studji b' Pegasys fuq it- tossiċità fuq is- sistema riproduttiva.
Treatment with interferon alfa-2a resulted in a statistically significant increase in abortifacient activity in rhesus monkeys.
Il- kura bl- interferon alfa- 2a irriżultat f’ żieda statistikament sinifikanti fin- numru ta ’ aborti fix- xadini rhesus.
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 effetti avversi fil- bniedem.
Pegasys plus ribavirin When used in combination with ribavirin, Pegasys did not cause any effects in monkeys not previously seen with either active substance alone.
Pegasys ma ’ ribavirin Meta użat flimkien ma ’ ribavirin, Pegasys ma ’ kellu l- ebda effett ieħor li ma kienx deher bl- użu taż - żewġ sustanzi waħidhom.
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, li s- severità tagħha kienet ogħla minn dik li sseħħ meta jingħataw xi wieħed mis- sustanzi attivi waħidhom.
sodium chloride polysorbate 80 benzyl alcohol (10 mg/ 1 ml) sodium acetate acetic acid water for injections
sodium chloride polysorbate 80 benzyl alcohol (10mg / 1 ml) sodium acetate acetic acid ilma għall- injezzjoni
The solution for injection is for single use only.
It- soluzzjoni għall- injezzjoni hija għall- użu ta ’ darba biss.
Any unused product or waste material should be disposed of in accordance with local requirements.
52 Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Pegasys 135 micrograms solution for injection in pre-filled syringe
Pegasys 135 mikrogramma soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest
One pre-filled syringe contains peginterferon alfa-2a*..................................................................... 135 micrograms Each syringe of 0.5 ml solution contains 135 micrograms peginterferon alfa-2a*.
Siringa waħda mimlija għal- lest fiha peginterferon alfa- 2a *............................................................................... 135 mikrogramma Kull siringa ta ’ 0. 5ml ta ’ soluzzjoni fiha 135 mikrogramma peginterferon alfa- 2a *.
*The active substance, peginterferon alfa-2a, is a covalent conjugate of the protein interferon alfa-2a produced by recombinant DNA technology in Escherichia coli with bis-[monomethoxy polyethylene glycol].
* Is- sustanza attiva, peginterferon alfa- 2a, hija konjugat kovalenti tal- proteina interferon alfa- 2a magħmula permezz ta ’ teknoloġija ta ’ DNA rikombinanti f’ Escherichia coli u kkonjugata ma ’ bis - [monomethoxy polyethylene glycol].
Solution for injection in pre-filled syringe.
Soluzzjoni għall- injezzjoni f’ siringa mimlija għal- lest.
54 4.2 Posology and method of administration
54 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Treatment should be initiated only by a physician experienced in the treatment of patients with hepatitis B or C.
Il- kura għandha tinbeda biss minn tabib li għandu esperjenza fil- kura ta ’ pazjenti li għandhom epatite B jew Ċ.
The dose of ribavirin to be used in combination with Pegasys s given in Table 1.
Id- doża ta ’ ribavirin li għandha tintuża meta jingħata flimkien ma ’ Pegasys hija mogħtija fit- Tabella 1.
55 Table 1:
55 Tabella 1:
Dosing Recommendations for Combination therapy for HCV Patients Genotype
Dożaġġi Rakkomandati għal Terapija Kombinata għall- Pazjenti b’ HCV Ġenotip Ġenotip 1 LVL
180 micrograms
Doża ta ’ Pegasys 180 mikrogramma
< 75 kg = 1000 mg ≥ 75 kg = 1200 mg
Doża ta ’ Ribavirin Tul < 75 kg = 1000 mg 24 ġimgħa jew ≥75 kg = 1200 mg
180 micrograms
b’ RVR *
Genotype 4 with RVR*
Ġenotip 1 HVL b’ RVR *
Genotype 2 or 3 without RVR**
Ġenotip 1 jew 4
800 mg
mingħajr RVR *
24 weeks
48 ġimgħa
A duration of therapy less than 48 weeks has not been adquately studied.
Tul ta ’ terapija ta ’ anqas minn 48 ġimgħa ma ġietx studjata biżżejjed.
Predictability of response and non-response – treatment-naïve patients Early virological response by week 12, defined as a 2 log viral load decrease or undetectable levels of HCV RNA has been shown to be predictive for sustained response (see Tables 2 and 6).
Tbassir ta ’ rispons u ta ’ nuqqas ta ’ rispons – pazjenti li qatt ma jkunu ħadu kura qabel Effett viroloġiku bikri sat- 12- il ġimgħa, definit bħala tnaqqis ta ’ 2 log fil- viral load jew livelli ta ’ HCV RNA li ma jitkejlux gie muri bħala indikattiv għal rispons sostenut (ara Tabelli 2 u 6).
56 Table 2:
56 Tabella 2.
Predictive Value of Week 12 Virological Response at the Recommended Dosing Regimen while on Pegasys Combination Therapy Genotype
Valur Predittiv għar- Rispons Viroloġika tat- 12- il Ġimgħa fid- Dożaġġi Rakkomendati waqt Terapija Kombinata ta ’ Pegasys Ġenotip
The negative predictive value for sustained response in patients treated with Pegasys in monotherapy was 98%.
Il- valur negattiv predittiv għal rispons sostenut f’ pazjenti kurati b’ monoterapija ta ’ Pegasys kien ta ’ 98%.
Dose increases to or towards the original dose may be considered when the adverse reaction abates (see section 4.4 for use and section 4.8).
Żidiet fid- doża lejn jew għal dik oriġinali jistgħu jiġu kkonsidrati meta ir- reazzjoni avversa tonqos (ara sezzjoni 4. 4 għall- użu u sezzjoni 4. 8).
Haematological (see also Table3) Dose reduction is recommended if the neutrophil count is < 750/ mm3.
Ematoloġiċi (ara wkoll Tabella 3) Tnaqqis fid- doża huwa rakkomandat jekk in- numru ta ’ newtrofili huwa < 750/ mm3.
(1) a patient without significant cardiovascular disease experiences a fall in haemoglobin to < 10 g/ dl and ≥ 8.5 g/ dl, or (2) a patient with stable cardiovascular disease experiences a fall in haemoglobin by ≥ 2 g/ dl during any 4 weeks of treatment.
(1) pazjent mingħajr ebda mard kardjovaskulari sinifikanti jkollu tnaqqis fil- livell ta ’ emoglobina għal < 10 g/ dl u ≥ 8. 5 g/ dl, jew (2) pazjent b’ mard kardjovaskulari stabbli jkollu tnaqqis fil- livell ta ’ emoglobina b ’ ≥ 2 g/ dl waqt kwalunkwe 4 ġimgħat ta ’ kura.
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.
57 600 milligramma kuljum, u tiġi miżjuda għal 800 milligramma kuljum skond id- diskrezzjoni tat- tabib responsabbli.
Combination
Waqqaf it -
to 600 mg
Ribavirin għal Ribavirin 600 mg
to 135/ 90/ 45 micrograms
Pegasys għal 135/ 90/ 45 mikrogrammi
Absolute Neutrophil Count
Numru Assolut ta ’ Newtrofili
< 50,000/mm3 > 25,000/ mm3
< 50, 000/ mm3
As with other alpha interferons, increases in ALT levels above baseline (BL) have been observed in patients treated with Pegasys, including patients with a virological response.
Bħal fl- użu ta ’ alfa interferons oħra, żidiet fil- livelli ta ’ ALT ’ l fuq mill- linja bażi (BL) dehru f’ pazjenti kkurati b' Pegasys, inklużi pazjenti b’ rispons viroloġiku.
For chronic hepatitis B patients, transient flares of ALT levels sometimes exceeding 10 times the upper limit of normal are not uncommon, and may reflect immune clearance.
Għall- pazjenti b’ epatite B kronika, żiediet għoljin temporanji fil- livelli ta ’ ALT li xi drabi jaqbżu b’ 10 darbiet l - ogħla limitu tan- normal m’ humiex rari u jistgħu jirriflettu t- tneħħija mis- sistema immuni.
Treatment should normally not be initiated if ALT is > 10 times the upper limit of normal.
Il - kura normalment m’ għandiex tinbeda jekk l- ALT huwa > 10 darbiet l - ogħla limitu tan- normal.
Consideration should be given to continuing treatment with more frequent monitoring of liver function during ALT flares.
Għandha tingħata konsiderazzjoni għat- tkomplija tal- kura b’ sorveljanza aktar frekwenti tal- funzjoni tal - fwied waqt iż- żiediet ta ’ ALT.
Patients under the age of 18 years The safety and efficacy of Pegasys have not been established in this population.
Pazjenti b’ età taħt it- 18- il sena Is- sigurtà u l- effikaċja ta ’ Pegasys f’ din il- popolazzjoni ma ġietx stabilita ’.
Regardless of the starting dose or degree of renal impairment, patients should be monitored and appropriate dose reductions of Pegasys during the course of therapy should be made in the event of adverse reactions.
58 jiġu monitorjati u għandu jkun hemm tnaqqis xieraq fid- doża ta ’ Pegasys matul it- terapija f’ każ ta ’ reazzjonijiet avversi.
58 Patients with hepatic impairment In patients with compensated cirrhosis (eg, Child-Pugh A), Pegasys has been shown to be effective and safe.
Pazjenti b’ indeboliment tal- fwied F’ pazjenti b’ ċirrożi kompensata (eż, Child- Pugh A), Pegays deher li huwa effettiv u mingħajr periklu.
The Child-Pugh classification divides patients into groups A, B, and C, or "Mild", "Moderate" and "Severe" corresponding to scores of 5-6, 7-9 and 10-15, respectively.
Il- klassifikazzjoni taċ- Child- Pugh taqsam il- pazjenti fi gruppi A, B, u Ċ, jew “ Ħafif ”, “ Moderat ” u “ Severa ” li jikkorrispondu għal punteġġ ta ’ 5- 6, 7- 9 u 10- 15, rispettivament.
Absent Slight Moderate
AssentiFtit Moderat
• 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
4. 3 Kontra- indikazzjonijiet • 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 b’ ċirrożi u punteġġ Child- Pugh ta ’ ≥ 6.
59 4.4 Special warnings and precautions for use
59 4. 4 Twissijietspeċjali u prekawzjonijiet għall- użu
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 sintomi bħal dawn jitfaċċaw, is- serjetà potenzjali ta ’ dawn l- effetti mhux mixtieqa trid tittieħed f’ konsiderazzjoni mit- tabib li qed jippreskrivi u għandu jiġi kkunsidrat l- bżonn ta ’ mmaniġġjar terapewtiku xieraq.
Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Il- linji gwida kurrenti dwar jekk hemmx bżonn ta ’ bijopsija tal- fwied qabel ma tinbeda l - kura għandhom jiġu kkonsultati.
60 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.
60 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.
The use of Pegasys and ribavirin combination therapy in chronic hepatitis C patients who failed prior treatment has not been adequately studied in patients who discontinued prior therapy for hematological adverse events.
L- użu ta ’ terapija kombinata ta ’ Pegasys u ribavirin f’ pazjenti b’ epatite Ċ kronika li fallew kura minn qabel ma ġietx studjata b’ mod adegwat f’ pazjenti li waqqfu l- kura ta ’ qabel minħabba avvenimenti avversi ematoloġiċi.
When the increase in ALT levels is progressive and clinically significant, despite dose reduction, or is accompanied by increased direct bilirubin, therapy should be discontinued (see sections 4.2 and 4.8).
Meta ż- żieda fil- livelli ta ’ ALT hija waħda progressiva u klinikament sinifikanti, minkejja t- tnaqqis fid- doża, jew ikun hemm ukoll żieda diretta ta ’ bilirubina, it- terapija għandha titwaqqaf (ara sezzjonijiet 4. 2u 4. 8).
Hypersensitivity Serious, acute hypersensitivity reaction (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been rarely observed during alpha interferon therapy.
Sensittività eċċessivaReazzjoni gravi ta ’ sensittività eccessiva akuta (eż, urtikarja, angjoedema, bronkokonstrizzjoni, anafilassi) kienu rarament osservati matul terapija b’ alpha interferons.
Transient rashes do not necessitate interruption of treatment.
Ma hemmx bżonn li titwaqqaf it- terapija f’ każ ta ’ raxx temporanju.
Patients predisposed to the development of autoimmune disorders may be at
Pazjenti li huma predisposti għall- iżvilupp ta ’ mard awtoimmuni jistgħu jkunu f’ riskju ogħla.
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).
61 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).
Fever/ infections While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of persistent fever, particularly serious infections (bacterial, viral, fungal) must be ruled out, especially in patients with neutropenia.
Deni/ infezzjonijiet Waqt li deni jista ’ jkun assoċċjat ma ’ sindromu li tixbaħ lill- influenza li hija ta ’ spiss rapportata waqt terapija b’ interferon, kawżi oħrajn ta ’ deni persistenti, partikolarment infezzjonijiet serji (ikkawżati minn batterja, virus, jew moffa) għandhom jiġu esklużi, speċjalment f’ pazjenti b’ newtropenja.
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 sarkojdosi, u f’ każijiet ta ’ fejn ikun hemm bidu ta ’ jew aggravar ta ’ feriti psorjatiċi, it- twaqqif tat- terapija għandu jiġi kkunsidrat.
Co-infected patients should be closely monitored, assessing their Child-Pugh score during treatment, and should be immediately discontinued if they progress to a Child-Pugh score of 7 or greater.
62 Pazjenti ko- infettati għandhom jiġu sorveljati bir- reqqa, il- punteġġ Child- Pugh għandu jiġi stmat waqt il- kura, u l- kura għandha titwaqqaf immedjatament jekk ikollhom punteġġ Child- Pugh ta ’ 7 jew ogħla.
62 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.
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.
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 theophylline u Pegasys flimkien.
HIV-HCV co-infected patients No apparent evidence of drug interaction was observed in 47 HIV-HCV co-infected patients who completed a 12 week pharmacokinetic substudy to examine the effect of ribavirin on the intracellular phosphorylation of some nucleoside reverse transcriptase inhibitors (lamivudine and zidovudine or stavudine).
63 Pazjenti ko- infettati b’ HIV- HCV Ma kienet osservata l- ebda evidenza apparenti ta ’ interazzjoni ta ’ mediċini f’ 47 pazjent ko- infettati b’ HIV- HCV li temmew substudju farmakokinetiku ta ’ 12- il ġimgħa li eżamina l- effett ta ’ ribavirin fuq il- fosforilizazzjoni intraċellolari ta ’ uħud mill- inibituri ta ’ nucleoside reverse transcriptase (lamivudine u zidovudine jew stavudine).
63 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 irrapportata 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.
Pegasys has a minor or moderate influence on the ability to drive and use machines.
Pazjenti li jiżviluppaw sturdament, konfużjoni, ngħas jew għeja għadhom ikunu avżati sabiex jevitaw li jsuqu jew iħaddmu xi magni.
Patients who develop dizziness, confusion, somnolence or fatigue should be cautioned to avoid driving or operating machinery.
Pegasys għandu effett żgħir jew moderat fuq il- ħila biex issuq u tħaddem magni.
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). The most frequently reported adverse reactions with Pegasys 180 micrograms were mostly mild to moderate in severity and were manageable without the need for modification of doses or discontinuation of therapy.
Ir- reazzjonijiet avversi li dehru l- aktar ta ’ spiss b' Pegasys 180 mikrogramma ġeneralment kienu ħfief għall- moderati fis- severità tagħhom u kienu kontrollati mingħajr ma kien hemm bżonn li tinbidel id- doża jew li titwaqqaf it- terapija.
Chronic hepatitis B
64 Epatite B kronika
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).
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).