qanastek/EMEA-V3 huggingface dataset:
Ribavirin 1000/ 1200 mg 48 weeks Interferon Pegylated interferon Interferon plus ribavirin Pegylated interferon plus ribavirin
23 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
23 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.
Sustained Virological Response based on Genotype and Pre-treatment Viral Load after Pegasys Combination Therapy with Ribavirin in HIV-HCV Co-infected Patients Study NR15961
Rispons Viroloġiku Sostenut ibbażat fuq Ġenotip u Viral Load ta ’ Qabel il- Kura wara Terapija Kombinata b’ Pegasys ma ’ Ribavirin f’ Pazjenti Ko- infettati b’ HIV- HCV Study NR15961
Interferon alfa-2a 3 MIU &
Interferon alfa- 2a 3 MIU &
Ribavirin 800 mg 48 weeks
Ribavirin 800 mg
Placebo 48 weeks
Plaċebo
Ribavirin 800 mg 48 weeks
48 ġimgħa
All patients
Pazjenti kollha
Genotype 1 Low viral load High viral load
Viral load baxxa Viral load għolja
Genotype 2-3 Low viral load High viral load
Viral load baxxa Viral load għolja
Low viral load= ≤ 800,000 IU/ mL; High viral load= > 800,000 IU/ mL * Pegasys 180 mcg ribavirin 800 mg vs.
Viral load baxxa= ≤ 800, 000 IU/ mL; Viral load għolja= > 800, 000 IU/ mL * Pegasys 180 mcg ribavirin 800mg vs.
Interferon alfa-2a 3MIU ribavirin 800 mg:
Interferon alfa- 2a 3MIU ribavirin 800mg:
Odds Ratio (95% CI) = 5.40 (3.42 to 8.54), …. P-value (stratified Cochran-Mantel-Haenszel test) = < 0.0001 * Pegasys 180 mcg ribavirin 800 mg vs.
Odds Ratio (95% CI) = 5. 40 (3. 42 sa 8. 54), … Valur- p (test Cochran- Mantel- Haenzel stratifikat) = < 0. 0001 * Pegasys 180 mcg ribavirin 800mg vs.
Pegasys 180μ g:
Pegasys 180μg,:
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.
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.
Odds Ratio (95% CI) = 0.53 (0.33 to 0.85), … P-value (stratified Cochran-Mantel-Haenszel test) = < 0.0084
Odds Ratio (95% CI) = 0. 53 (0. 33 sa 0. 85), … Valur- p (test Cochran- Mantel- Haenzel stratifikat) = < 0. 0084
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 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.
The SVRs reported in the treatment arms of this study were similar to the corresponding treatment arms from study NV15942.
SVRs irrapportati fil - gruppi ta ’ kura ta ’ dan l- istudju kienu simili għall- gruppi ta ’ kura korrispondenti mill- istudju NV15942.
Following a single subcutaneous injection of Pegasys 180 micrograms in healthy subjects, serum concentrations of peginterferon alfa-2a are measurable within 3 to 6 hours.
Wara injezzjoni waħda minn taħt il- ġilda ta ’ Pegasys 180 mikrogramma f’ individwi b’ saħħithom, il - konċentrazzjonijiet fis- serum ta ’ peginterferon alfa- 2a jistgħu jibdew jitkejlu fi żmien 3 sa 6 sigħat.
Within 24 hours, about 80% of the peak serum concentration is reached.
Fi żmien 24 siegħa tintlaħaq, madwar 80% tal- konċentrazzjoni massima fis- serum.
The absorption of Pegasys is sustained with peak serum concentrations reached 72 to 96 hours after dosing.
L- assorbiment ta ’ Pegasys jinżamm, b’ konċentrazzjoni massima fis- serum tintlħaq bejn 72 u 96 il- siegħa wara li tingħata
The absolute bioavailability of Pegasys is 84% and is similar to that seen with interferon alfa-2a.
Il- biodisponibiltà assoluta ta ’ Pegasys hija ta ’ 84% u hija simili għal dik osservata b’ interferon alfa- 2a.
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.
Peginterferon alfa- 2a jinstab l- aktar 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- bilanċ tal- piż, distribuzzjoni fit- tessuti u awtoradjuluminografija tal- ġisem kollu li saru fil - firien, peginterferon alfa- 2a jinfirex fil- fwied, kliewi u fil- mudullun ta ’ l- għadam minbarra li huwa konċentrat 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 involuta fit- tneħħijja ta ’ materjal radjutikkettat.
In humans, the systemic clearance of peginterferon alfa-2a is about 100-fold lower than that of the native interferon alfa-2a.
Fil- bniedem, ir- rata tat - tneħħijja sistemika ta ’ peginterferon alfa- 2a hija bejn wieħed u ieħor 100 darba aktar baxxa minn dik ta ’ interferon alfa- 2a li jiġi prodott fil- ġisem.
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- vina, il- half life terminali ta ’ peginterferon alfa- 2a f’ soġġetti b’ saħħithom hija ta ’ bejn madwar 60 sa 80 siegħa mqabbel ma ’ valuri ta ’ 3 sa 4 sigħat 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 siegħa (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 wkoll l- assorbiment sostenut ta ’ Pegasys.
24 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.
Iż- żidiet fl- espożizzjoni għal Pegasys kienu proporzjonali mad- doża f’ individwi b’ saħħithom u f’ pazjenti b’ epatite B jew Ċ kronika wara doża 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 b’ 2 sa 3 darbiet aktar wara li ngħataw doża darba fil- ġimgħa għal 6 sa 8 ġimgħat meta mqabbla ma ’ figuri ta ’ doża waħda.
There is no further accumulation after 8 weeks of once weekly dosing.
M’ hemmx aktar akkumulazzjoni wara 8 ġimgħat b’ dożi 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 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 jibqgħu l- istess għal ġimgħa sħiħa (168 siegħa).
Patients with renal impairment Renal impairment is associated with slightly decreased CL/ F and prolonged half-life.
Pazjenti b’ insuffiċjenza renali Insuffiċjenza renali hija assoċjata ma ’ tnaqqis żgħir fil- CL/ F u ma ’ żieda fil- half life.
In patients (n=3) with CLcrea between 20 and 40 ml/ min, the average CL/ F is reduced by 25% compared with patients with normal renal function.
F’ pazjenti (n=3) b’ CLcrea ta ’ bejn 20 u 40 ml/ min, il- medja ta ’ CL/ F tonqos b’ 25% meta mqabbla ma ’ pazjenti b’ funzjoni renali normali.
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 ’ 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).
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 individwi maskili u femminili b’ saħħithom.
Elderly In subjects older than 62 years, the absorption of Pegasys after a single subcutaneous injection of 180 micrograms was delayed but still sustained compared to young healthy subjects (tmax of 115 hours vs.
Anzjani F’ individwi li għandhom aktar minn 62 sena, l- assorbiment ta ’ Pegasys wara injezzjoni waħda minn taħt il- ġilda ta ’ 180 mikrogramma kien ritardat iżda baqgħa l- istess meta mqabbel ma ’ dak f’ pazjenti b’ saħħithom iżgħar (tmas ta ’ 115 siegħa vs.
82 hours, older than 62 years vs. younger, respectively).
82 siegħa, anzjani ta ’ aktar minn 62 sena vs. iżgħar, rispettivament).
The AUC was slightly increased (1663 vs.
L- AUC kienet kemmxejn ogħla (1663 vs.
1295 ng·h/ ml) but peak concentrations (9.1 vs.
1295 ng. h/ ml) iżda l- konċentrazzjonijiet massimi (9. 1 vs.
10.3 ng/ ml) were similar in subjects older than 62 years.
10. 3 ng/ ml) kienu simili f’ individwi li għandhom aktar minn 62 sena.
Based on drug exposure, pharmacodynamic response and tolerability, a lower dose of Pegasys is not needed in the geriatric patient (see section 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 komparabbli 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 kif 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.
25 Waqt studji kien hemm tnaqqis fl- espożizzjoni għal Pegasys meta ingħata fid- dirgħajn meta mqabbel ma ’ għotja fl- addome u fil- koxxa.
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 kienu limitati minħabba l- ispeċifiċità ta ’ l - interferons għall- 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 r- riżultati li dehru fl- annimali li ngħatalhom peginterferon kienu simili għal dawk li nkisbu minn interferon alfa- 2a.
Reproductive toxicity studies have not been performed with Pegasys.
Ma sarux studji b' Pegasys għat- tossiċità fuq is- sistema riproduttiva.
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 peginterferon alfa- 2a lil xadini ta ’ sess femminili.
Treatment with interferon alfa-2a resulted in a statistically significant increase in abortifacient activity in rhesus monkeys.
Il- kura b’ 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- bnedmin.
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 wżat flimkien ma ’ ribavirin, Pegasys ma ’ kellu l- ebda effett ieħor li ma deherx 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- akbar 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 polisorbate 80 benzyl alcohol (10mg / 1 ml) sodium acetate acetic acid ilma għall- injezzjonijiet
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Minħabba li ma sarux studji li juru liema huma l- prodotti li ma ’ jaqblux miegħu, dan il- prodott mediċinali m’ għandux jiġi mħallat ma ’ prodotti mediċinali oħrajn.
Do not freeze.
Aħżen fi friġġ (2°C – 8°C). Tagħmlux fil- friża.
1 ml of solution for injection in vial (siliconised Type I glass) with stopper (rubber butyl).
1 ml ta ’ soluzzjoni għall- injezzjoni ġo kunjett (ħġieġ tat- Tip I silikonizzat) b’ tap (butyl tal- gomma).
Available in packs of 1 or 4.
Disponibbli f’ pakketti ta ’ 1 jew 4.
Not all pack-sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
The solution for injection is for single use only.
It- soluzzjoni għall- injezzjonijiet hija għall- użu ta ’ darba biss.
It should be inspected visually for particulate matter and discoloration before administration.
Għandha tiġi eżaminata viżwalment għall - frak u għal telf ta ’ kulur qabel ma tingħata.
Any unused product or waste material should be disposed of in accordance with local requirements.
26 Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa ’ wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City Hertfordshire AL7 1TW Ir- Renju Unit
20 June 2002/ 20 June 2007
20 ta ’ Ġunju 2002 / 20 ta ’ Ġunju 2007
Pegasys 180 micrograms solution for injection
Pegasys 180 mikrogramma soluzzjoni għall- injezzjoni
peginterferon alfa-2a*.................................................................................... .180 micrograms Each vial of 1 ml solution contains 180 micrograms peginterferon alfa-2a*.
peginterferon alfa- 2a *............................................................................... 180 mikrogramma Kull kunjett ta ’ 1 ml ta ’ soluzzjoni fih 180 mikrogramma peginterferon alfa- 2a *.
The strength indicates the quantity of the interferon alfa-2a moiety of peginterferon alfa-2a without consideration of the pegylation.
Il- qawwa tindika l - kwantità tal- parti ta ’ interferon alfa- 2a ta ’ peginterferon alfa- 2a mingħajr konsiderazzjoni tal - pegilazzjoni. * 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].
*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].
Dan jirriżulta f’ piż molekulari ta ’ madwar 60 kDa.
The solution is clear and colourless to light yellow.
It- soluzzjoni hija ċara u mingħajr kulur għal isfar ċar.
Pegasys is indicated for the treatment of HBeAg-positive or HBeAg-negative chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication, increased ALT and histologically verified liver inflammation and/ or fibrosis (see sections 4.4 and 5.1).
Pegasys huwa indikat għall- kura ta ’ epatite B kronika pożittiva għal HBeAg jew negattiva għal HBeAg f’ pazjenti adulti b’ mard kumpensat tal- fwied u b’ evidenza ta ’ replikazzjoni virali, żieda fl- ALT u infjammazzjoni tal- fwied verifikata b’ mod istoloġiku u/ jew fibrożi (ara sezzjonijiet 4. 1 u 5. 1).
Monotherapy is indicated mainly in case of intolerance or contraindication to ribavirin.
Monoterapija hija indikata prinċiparjament f’ każ ta ’ intolleranza jew fejn hemm kontra- indikazzjoni għar- ribavirin.
28 4.2 Posology and method of administration
28 4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Please refer also to the ribavirin Summary of Product Characteristics (SPC) when Pegasys is to be used in combination with ribavirin.
Jekk jogħġbok irreferi ukoll għas- Sommarju tal- Karatteristiċi tal- Prodott (SPC) ta ’ ribavirin meta Pegasys jkun ser jintuża ’ flimkien ma ’ ribavirin.
The recommended dose for Pegasys is 180 micrograms once weekly by subcutaneous administration in the abdomen or thigh given in combination with oral ribavirin or as monotherapy.
Id- doża ta ’ Pegasys rakkomandata hija ta ’ 180 mikrogramma darba fil- ġimgħa permezz ta ’ għotja minn taħt il- ġilda fl- addome jew fil- koxxa f’ taħlita ma ’ ribavirin li jittieħed mill- ħalq, jew bħala monoterapija.
The dose of ribavirin to be used in combination with Pegasys is given in Table 1.
Id- doża ta ’ ribavirin li għandha tintuża meta jingħata flimkien ma ’ Pegasys hija mogħtija fit- Tabella 1.
The duration of combination therapy with ribavirin for chronic hepatitis C depends on viral genotype.
It- tul tat- terapija imħalta ma ’ ribavirin għall- epatite Ċ kronika tiddependi fuq il- ġenotip tal- virus.
However, an overall 24 weeks treatment duration may be associated with a higher risk of relapse than a 48 weeks treatment duration (see section 5.1).
Iżda, tul ta ’ kura totali ta ’ 24 ġimgħa jista ’ jkun assoċjat ma ’ riskju għola li l- pazjent jirkadi meta mqabbel ma ’ tul ta ’ kura ta ’ 48 ġimgħa (ara sezzjoni 5. 1).
29 Table 1:
29 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 rapidu (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
The recommended duration of Pegasys monotherapy is 48 weeks.
It- tul rakkomandat ta ’ monoterapija b' Pegasys huwa ta ’ 48 ġimgħa.
A duration of therapy less than 48 weeks has not been adequately 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 viroloġika bikrija sa ġimgħa 12, definita bħala tnaqqis ta ’ 2 log fil- viral load jew livelli ta ’ HCV RNA li ma jitkejlux ġiet murija bħala indikattiva għal rispons sostenut (ara Tabelli 2 u 6).
Predictive Value of Week 12 Virological Response at the Recommended Dosing Regimen while on Pegasys Combination Therapy Genotype
Valur Preditt għar- Rispons Viroloġika tat- 12- il Ġimgħa fil- Kors ta ’ Dożaġġ Rakkomendat waqt Terapija Kombinata ta ’ Pegasys Ġenotip
Negative
Negattiva Ebda
Positive
Ebda
response
Valur
Response
Pożittiva Rispons sat -
by
Risponss Valur ostenut Predittiv
week 12
rispons sat - 12- il ġimgħa
sustained response
rispons sostenut
Sustained response
Predittiv
Predictive Value
12- il ġimgħa
271
271 58%
Genotype 2 and 3
(N=569) Ġenotip 2 u 3
100%
(97/ 102) 100%
87%
(271/ 467) 87%
(3/ 3) 93
(3/ 3)
81
81 (81/ 93)
30 The negative predictive value for sustained response in patients treated with Pegasys in monotherapy was 98%.
Il- valur preditt negattiv għal rispons sostenut f’ pazjenti kurati b’ monoterapija ta ’ Pegasys kien ta ’ 98%.
Positive predictive values of 45% (50/ 110) and 70% (59/ 84) were observed for genotype 1 and genotype 2/ 3 HIV-HCV co-infected patients receiving combination therapy.
Figuri mbassra pożittvi ta ’ 45% (50/ 110) u 70% (59/ 84) kienu osservati f’ pazjenti ko - infettati b’ HIV- HCV ta ’ ġenotip 1 u ġenotip 2/ 3 li kienu qed jirċievu terapija kombinata.
Dose adjustment for adverse reactions
Tibdil fid -- doża minħabba reazzjonijiet avversi
General Where dose adjustment is required for moderate to severe adverse reactions (clinical and/ or laboratory) initial dose reduction to 135 micrograms is generally adequate.
Ġenerali Meta jkun hemm bżonn ta ’ aġġustament fid- doża minħabba reazzjonijiet avversi moderati jew severi (kliniċi u/ jew fil- laboratorju) tnaqqis inizjali għal doża ta ’ 135 mikrogramma huwa ġeneralment adegwat.
However, in some cases, dose reduction to 90 micrograms or 45 micrograms is necessary.
Iżda, f’ xi każijiet, tnaqqis fid- doża għal 90 mikrogramma jew 45 mikrogramma huwa neċessarju.
Dose increases to or towards the original dose may be considered when the adverse reaction abates (see sections 4.4 and 4.8).
Żidiet fid- doża lejn jew għal dik oriġinali jistgħu jiġu kkonsidrati meta ir- reazzjoni avversa tonqos (ara sezzjonijiet 4. 4 u 4. 8).
For patients with Absolute Neutrophil Count (ANC )< 500/mm3 treatment should be suspended until ANC values return to > 1000/mm3.
Il- kura għandha titwaqqaf f’ pazjenti li għandhom Numru Assolut ta ’ Newtrofili (ANC) < 500/ mm3 sakemm il- valuri ta ANC jerġgħu jitilgħu għal > 1000/ mm3.
Therapy should initially be re-instituted at 90 micrograms Pegasys and the neutrophil count monitored.
It- terapija għandha terġa ’ tinbeda b’ doża ta ’ 90 mikrogrammi ta ’ Pegasys u l- livelli ta ’ newtrofili għandhom jiġu monitorati.
Dose reduction to 90 micrograms is recommended if the platelet count is < 50,000/ mm3.
Huwa rakkomandat li d- doża titnaqqas għal 90 mikrogrammi jekk in- numru ta ’ plejtlits huwa < 50, 000/ mm3.
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:
(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 tat- kura.
(1) A patient without significant cardiovascular disease experiences a fall in haemoglobin confirmed to < 8.5 g/ dl; (2) A patient with stable cardiovascular disease maintains a haemoglobin value < 12 g/ dl despite 4 weeks on a reduced dose.
(1) pazjent mingħajr ebda mard kardjovaskulari sinifikanti li jkollu tnaqqis fil- livell ta ’ emoglobina ikkonfermat għal < 8. 5 g/ dl; (2) pazjent b’ mard kardjovaskulari stabbli li jżomm livell ta ’ emoglobina ta ’ < 12 g/ dl avolja jkun għamel 4 ġimgħat fuq doża imnaqqsa.
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.
31 600 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)
Tibdil fid- Doża għal Reazzjonijiet Avversi (Għal aktar informazzjoni ara l- kitba ta ’ hawn fuq)
Combination
Terpaija Kombinata
Haemoglobin - no cardiac disease
plejtlits Emoglobina - ebda marda kardijaka
10 g/ dl, and < 8.5 g/ dl 8.5 g/ dl
< 10 g/ dl, and < 8. 5 g/ dl ≥ 8. 5 g/ dl
Haemoglobin
> 25, 000/ mm
stable cardiac disease
Emoglobina - marda kardijaka stabbli
≥ 2 g/ dl during any 4 weeks
Tnaqqis ≥ 2 < 12 g/ dl g/ dl waqt avolja trattat kwalunkwe 4 għal 4 ġimgħat ġimgħat b’ doża imnaqqsa
In case of intolerance to ribavirin, Pegasys monotherapy should be continued.
F’ Każ ta ’ intolleranza għal ribavirin, monoterapija ta ’ Pegasys għandha titkompla.
In chronic hepatitis C clinical trials, isolated increases in ALT (≥ 10x ULN, or ≥ 2x BL for patients with a BL ALT ≥ 10x ULN) which resolved without dose-modification were observed in 8 of 451 patients treated with combination therapy.
Fi provi kliniċi b’ epatite Ċ kronika, żidiet isolati fl- ALT (≥ 10x ULN, jew ≥ 2x BL għall- pazjenti li għandhom BL ALT ≥ 10x ULN) li rrisolvew ruħhom mingħajr ebda tibdil fid- doża kienu osservati fi 8 minn 451 pazjent ikkurati b’ terapija kombinata.
If ALT increase is progressive or persistent, the dose should be reduced initially to135 micrograms.
Jekk iż- żieda fl- ALT hija waħda progressiva jew persitenti, id- doża għandha titnaqqas inizjalment għal 135 mikrogrammi.
If the Pegasys dose is reduced or withheld, therapy can be restored once the flare is subsiding (see section 4.4).
Jekk id- doża ta ’ Pegasys titnaqqas jew titwaqqaf, it- terapija tista ’ terġa ’ titkompla la darba iż- żieda fil- livelli ta ’ ALT tibda tbatti (ara sezzjoni 4. 4).
Elderly Adjustments in the recommended dosage of 180 micrograms once weekly are not necessary when instituting Pegasys therapy in elderly patients (see section 5.2).
Anzjani Ma hemmx bżonn ta ’ tibdil fid- doża rakkomandata ta ’ 180 mikrogramma fil- ġimgħa meta tinbeda terapija b' Pegasys f’ pazjenti anzjani (ara sezzjoni 5. 2).
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.
Pegasys is contraindicated in neonates and young children up to 3 years old, because of the excipient benzyl alcohol (see section 4.3 and 4.4).
Pegasys huwa kontra- indikat fi trabi tat- twelied u tfal żgħar sa età ta ’ 3 snin, minħabba s- sustanza mhux attiva benzyl alcohol (ara sezzjoni 4. 3 u 4. 4).
Patients with renal impairment In patients with end stage renal disease, a starting dose of 135 micrograms should be used (see section 5.2).
Pazjenti b’ indeboliment tal- kliewi F’ pazjenti b’ marda tal- kliewi ta ’ l- aħħar stadju, għandha tintuża doża inizjali ta ’ 135 mikrogramma (ara sezzjoni 5. 2).
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.
Irrespettivament mid- doża inizjali jew mill- livell ta ’ ħsara fil- kliewi, il- pazjenti għandhom
32 Patients with hepatic impairment In patients with compensated cirrhosis (eg, Child-Pugh A), Pegasys has been shown to be effective and safe.
32 jiġu monitorjati u għandu jkun hemm tnaqqis xieraq fid- doża ta ’ Pegasys matul it- terapija f’ każ ta ’ reazzjonijiet avversi.
Pegasys has not been evaluated in patients with decompensated cirrhosis (eg, Child-Pugh B or C or bleeding oesophageal varices) (see section 4.3).
Pegasys ma ġiex evalwat f’ pazjenti b’ ċirrożi dekompensata (eż, Child- Pugh B jew Ċ jew bleeding oesophageal varices) (ara sezzjoni 4. 3).
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 Child- Pugh taqsam il- pazjenti fi gruppi A, B, u Ċ, jew “ Ħafif ”, “ Moderat ” u “ Sever ” li jikkorrispondu għal punteġġ ta ’ 5- 6, 7- 9 u 10- 15, rispettivament.
Modified Assessment Assessment Encephalopathy
Assessjar Modifikat Assessjar Enċefalopatija
Degree of abnormality None Grade 1-2 Grade 3-4*
Grad ta ’ anormalita ’ Ebda Grad 1- 2 Grad 3- 4 *
Score 1 2 3
Punti 1 2 3 1
Ascites
Axxite
Absent Slight Moderate
Assenti Ftit Moderat
S-Bilirubin (mg/ dl)
Bilirubina- S (mg/ dl)
< 2 2.0- 3> 3
< 2 2. 0- 3 > 3
S-Albumin (g/ dl)
< 34 2 34- 51 3 > 51 1 Albumina- S (g/ dl)
• 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 li għandhom ċirrożi u punteġġ Child- Pugh ta ’ ≥ 6.
Other CNS effects including aggressive behaviour (sometimes directed against others), confusion and alterations of mental status have been observed with alpha interferons.
Effetti oħra tas- CNS inkluż mġieba aggressiva (xi kultant lejn oħrajn), konfużjoni u tibdil fl- istat mentali kienu osservati b ’ alpha interferons.
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.
33 trid tittieħed f’ konsiderazzjoni mit- tabib li qed jippreskrivi u għandu jiġi kkunsidrat l- bżonn ta ’ mmaniġġjar terapewtiku xieraq.
If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with Pegasys be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Jekk is- sintomi psikjatriċi jippersistu jew imorru għal agħar, jew jiġi identifikat ħsieb ta ’ suwiċidju, huwa rakkomandat li l- kura b’ Pegasys titwaqqaf, u l- pazjent jiġi segwit b’ intervent psikjatriku kif jixraq.
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (ie, patients with genotype 2 or 3), treatment may be possible without histological confirmation.
Il- pazjenti kollha fl- istudji ta ’ l- epatite kronika Ċ saritilhom bijopsija tal- fwied qabel ma bdew it - terapija, iżda f’ xi każi (jiġifieri, pazjenti bil- ġenotip 2 jew 3), il- kura hija possibli mingħajr konferma istoloġika.
Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Il- linji gwida kurrenti fuq jekk hemmx bżonn ta ’ bijopsija tal- fwied qabel ma jinbeda l- kura għandhom jiġu kkonsultati.
- Adequately controlled thyroid function (TSH and T4).
- Funzjoni tat- tirojde kontrollata kif jixraq (TSH u T4)
In clinical trials, Pegasys treatment was associated with decreases in both total white blood cell (WBC) count and absolute neutrophil count (ANC), usually starting within the first 2 weeks of treatment (see section 4.8).
Fil- provi kliniċi, kura b' Pegasys kien assoċċjat ma ’ tnaqqis fin- numru totali ta ’ ċelloli bojod tad- demm (WBC) u fin- Numru Assolut ta ’ Newtrofili (ANC), li ssoltu jidhru fl- ewwel ġimagħtejn (2) ta ’ kura (ara sezzjoni 4. 8).
Progressive decreases after 8 weeks of therapy were infrequent.
Tnaqqis progressiv wara 8 ġimgħat ta ’ terapija kien 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.
Pegasys treatment has been associated with decreases in platelet count, which returned to pre- treatment levels during the post-treatment observation period (see section 4.8).
Kura b' Pegasys kienet assoċċjata ma ’ tnaqqis fin- numru ta ’ plejtlits, li rrittornaw għall- livelli ta ’ qabel il- kura fil- perijodu ta ’ osservazzjoni ta ’ wara l- kura (ara sezzjoni 4. 8).
In some cases, dose modification may be necessary (see section 4.2).
F’ xi każi, tibdil tad- doża tista ’ tkun neċessarja (ara sezzjoni 4. 2).
34 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.
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 frequency depends on the treatment duration and the dose of ribavirin (see section 4.8,).
Il- frekwenza tiddependi fuq it- tul ta ’ kemm iddum il- kura u fuq id- doża ta ’ ribavirin (ara sezzjoni 4. 8).
As with other interferons, caution should be exercised when administering Pegasys in combination with other potentially myelosuppressive agents.
Bħal fl- użu ta ’ interferons oħra, għandu jkun hemm attenzjoni meta Pegasys jingħata flimkien ma ’ sustanzi oħra b’ potenzjal majelosoppressiv.
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.
34 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.
TSH levels should be determined during the course of therapy if a patient develops clinical symptoms consistent with possible thyroid dysfunction (see section 4.8).
Il- livelli ta ’ TSH għandhom jitkejlu matul it- terapija jekk pazjent jiżviluppa sintomi kliniċi konsistenti ma ’ possibiltà ta ’ disfunzjoni tat- tirojde (ara sezzjoni 4. 8).
Cardiovascular system Hypertension, supraventricular arrhythmias, congestive heart failure, chest pain and myocardial infarction have been associated with alpha interferon therapies, including Pegasys.
Sistema kardjovaskulari Pressjoni għolja, aritmija supraventrikolari, insuffiċjenza tal- qalb konġestiva, uġigħ fis- sider u infart mijokardijaku kienu assoċjati ma ’ terapiji b’ alpha interferons, inkluż Pegasys.
In patients with cardiovascular disease, anaemia may necessitate dose reduction or discontinuation of ribavirin (see section 4.2).
F’ pazjenti b’ mard kardjovaskulari, anemija tista ’ jkollha bżonn tnaqqis fid- doża jew li jitwaqqaf ribavirin (ara sezzjoni 4. 2).
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. 2 u 4. 8).
In approximately half the case of flares exceeding 10 times the upper limit of normal, Pegasys dosing was reduced or withheld until the transaminase elevations subsided, while in the rest therapy was continued unchanged.
F’ madwar nofs il- każijiet ta ’ żiediet li kienu għola minn 10 darbiet l- għola livell tan- normal, id- dożaġġ ta ’ Pegasys kien imnaqqas jew imwaqqaf sakemm iż- żiediet fit- transaminase tbaxxew, filwaqt li l- bqija tat- terapija tkompliet mingħajr bidla.
Hypersensitivity Serious, acute hypersensitivity reaction (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been rarely observed during alpha interferon therapy.
Sensittività eċċessiva Reazzjoni gravi ta ’ sensittività eccessiva akuta (eż, urtikarja, angjoedema, bronkokonstrizzjoni, anafilassi) kienu rarament osservati matul terapija b’ alpha interferons.
If this occurs, therapy must be discontinued and appropriate medical therapy instituted immediately.
Jekk dan iseħħ, it- terapija għandha titwaqqaf u tingħata kura medika xierqa mmedjatament.
Transient rashes do not necessitate interruption of treatment.
Ma hemmx bżonn li titwaqqaf it - terapija f’ każ ta ’ raxx temporanju.
Autoimmune disease The development of auto-antibodies and autoimmune disorders has been reported during treatment with alpha interferons.
Mard awtoimmuni L- iżvilupp ta ’ awto- antikorpi u ta ’ mard awtoimmuni deher waqt kura b’ alpha interferons.
Patients predisposed to the development of autoimmune disorders may be at
Deni/ infezzjonijiet Waqt li deni jista ’ jkun assoċċjat ma ’ sindromu li tixbaħ l- influenza li hija ta ’ spiss rapportata waqt terapija b’ interferon, kawżi oħrajn ta ’ deni persistenti, partikolarment infezzjonijiet serji (ikkawżati
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).
35 minn batterja, virus, jew moffa) għandhom jiġu esklużi, speċjalment f’ pazjenti b’ newtropenja.
Appropriate anti-infective therapy should be started immediately and discontinuation of therapy should be considered.
Terapija anti- infettiva xierqa għandha tinbeda minnufiħ u t- twaqqif tat - terapija għandu jiġi kkunsidrat.
Ocular changes As with other interferons retinopathy including retinal haemorrhages, cotton wool spots, papilloedema, optic neuropathy and retinal artery or vein obstruction which may result in loss of vision have been reported in rare instances with Pegasys.
Tibdil okulari Bħall- interferons oħra, retinopatija inkluż emoraġija tar- retina, cotton wool spots, papilloedima, newropatija ottika u ostruzzjoni tal- vina jew arterja tar- retina li jistgħu jwasslu għal telf tal- vista dehru f’ każijiet rari b' Pegasys.
All patients should have a baseline eye examination.
Il- pazjenti kollha għandhom jagħmlu eżaminazzjoni bażika ta ’ l- għajnejn.
Patients with preexisting ophthalmologic disorders (eg, diabetic or hypertensive retinopathy) should receive periodic ophthalmologic exams during Pegasys therapy.
Pazjenti b’ mard oftalmoloġiku eżistenti minn qabel (eż, dijabete jew retinopatija ipertensiva) għandhom jirċievu perjodikament visti oftalmoloġiċi waqt terapija b' Pegasys.
Pegasys treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.
Il- kura b' Pegasys għandha titwaqqaf f’ pazjenti li jiżviluppaw mard oftalmoloġiku ġdid jew jekk il- mard oftalmoloġiku jmur għall - agħar.
Pulmonary changes As with other alpha interferons, pulmonary symptoms, including dyspnoea, pulmonary infiltrates, pneumonia, and pneumonitis have been reported during therapy with Pegasys.
Tibdil pulmonari Bħall- alpha interferons oħra, sintomi pulmonari, inkluż qtugħ ta ’ nifs, infiltrati pulmonari, pnewmonja, u pulmonite dehru waqt terapija b' Pegasys.
In case of persistent or unexplained pulmonary infiltrates or pulmonary function impairment, treatment should be discontinued.
F’ każ ta ’ infiltrati pulmonari jew problemi fil- funzjoni pulmonari persistenti jew inspjegabbli, il- kura għandha titwaqqaf.
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 jkun hemm bidu ta ’ jew aggravar ta ’ feriti psorjatiċi, it- twaqqif tat- terapija għandu jiġi kkunsidrat.
Transplantation The safety and efficacy of Pegasys treatment have not been established in patients with liver transplantation.
Trappjant Is- sigurtà u l- effikaċja ta ’ kura b’ pegasys ma ġewx stabiliti f’ pazjenti li rċevew trappjant tal- fwied.
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/ HAART) jistgħu jkunu f’ riskju akbar li jiżviluppaw aċidożi lattika.
Co-infected patients with advanced cirrhosis receiving HAART may also be at increased risk of hepatic decompensation and possibly death if treated with ribavirin in combination with interferons, including Pegasys.
Pazjenti ko- infettati b’ ċirrożi avvanzata li qed jirċievu HAART jistgħu jkunu ukoll f’ riskju ikbar ta ’ dekompensazzjoni epatika u possibilment mewt jekk jingħataw ribavirin flimkien ma ’ interferon, inkluż Pegasys.
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).
36 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.
Dental and periodontal disorders Dental and periodontal disorders, which may lead to loss of teeth, have been reported in patients receiving Pegasys and ribavirin combination therapy.
36 Disturbi dentali u paradentali Disturbi dentali u paradentali, li jistgħu jwasslu għal telf ta ’ snien, kienu rrapportati f’ pazjenti li rċevew terapija kombinata ta ’ Pegasys u ribavirin.
Patients should brush their teeth thoroughly twice daily and have regular dental examinations.
Il- pazjenti għandhom jaħslu snienhom sew darbtejn kuljum u jkollhom eżaminazzjonijiet dentali regolari.
Administration of Pegasys 180 micrograms once weekly for 4 weeks in healthy male subjects did not show any effect on mephenytoin, dapsone, debrisoquine and tolbutamide pharmacokinetics profiles, suggesting that Pegasys has no effect on in vivo metabolic activity of cytochrome P450 3A4, 2C9, 2C19 and 2D6 isozymes.
L- għotja ta ’ Pegasys 180 mikrogrammi darba fil- ġimgħa għal 4 ġimgħat f’ individwi maskili b’ saħħithom ma wriet l- ebda effett fuq il- profili farmakokinetiċi ta ’ mephenytoin, dapsone, debrosquine u tolbutamide, li tissuġġerixxi li Pegasys m’ għandu l- ebda effett fuq l- attivita ’ metabolika in vivo ta ’ isożimi taċ- ċitokromju P450 3A4, 2Ċ9, 2Ċ19 u 2D6.
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 aġġustasmenti 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).
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).
37 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.
37 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.
Use with ribavirin Significant teratogenic and/ or embryocidal effects have been demonstrated in all animal species exposed to ribavirin.
L- użu ma ’ ribavirin Effetti teratoġeniċi sinifikanti u/ jew effetti embrijoċidi dehru f’ kull speċji ta ’ annimal li kien espost għall- ribavirin.
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 fis- sieħba ta ’ pazjenti maskili li qed jieħdu Pegasys f’ taħlita ma ’ 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- sieħeb tagħhom għandhom jużaw kontraċettiv effettiv kull wieħed, waqt il- kura u għal 4 xhur wara li tintemm il- kura.
In clinical trials of 48 week treatment and 24 weeks follow-up, the safety profile for Pegasys in chronic hepatitis B was similar to that seen in chronic hepatitis C.
Epatite B kronika Fi provi kliniċi ta ’ 48 ġimgħa ta ’ kura u 24 ġimgħa ta ’ wara, il- profil ta ’ sigurtà ta ’ Pegasys f’ epatite B kronika kien simili għal dak li deher f’ epatite Ċ kronika.