qanastek/EMEA-V3 huggingface dataset:
Rebetol is indicated, in combination with interferon alfa-2b, for the treatment of adult patients with chronic hepatitis C, not previously treated, without liver decompensation, with elevated alanine aminotransferase (ALT), who are positive for serum HCV-RNA (see section 4.4).
Pazjenti ġodda għall- kura Pazjenti adulti: Rebetol huwa indikat għall- użu, flimkien ma ’ interferon alfa- 2b, għall- kura ta ’ pazjenti adulti b’ epatite C kronika, li ma kinux ikkurati qabel, mingħajr fwied mhux kumpensat, b’ alanine aminotransferase (ALT) għolja, li huma pożittivi għall- HCV- RNA fis- serum (ara sezzjoni 4. 4).
Additionally, Rebetol is indicated, in combination with peginterferon alfa-2b, for the treatment of adult patients with chronic hepatitis C, not previously treated, without liver decompensation, with elevated alanine aminotransferase (ALT), who are positive for serum HCV-RNA, including patients with clinically stable HIV co-infection (see section 4.4).
Minbarra hekk, Rebetol huwa indikat, f’ kombinazzjoni ma ’ peginterferon alfa- 2b, għall- kura ta ’ pazjenti adulti b’ epatite C kronika, li ma kienux ikkurati qabel, mingħajr fwied mhux kompensat, b’ alanine aminotransferase (ALT) għolja, li huma pożittivi għall- HCV- RNA fis- serum, inklużi pazjenti b’ ko- infezzjoni ta ’ HIV klinikament stabbli (ara sezzjoni 4. 4).
Rebetol is intended for use, in a combination regimen with interferon alfa- 2b, for the treatment of children and adolescents 3 years of age and older, who have chronic hepatitis C, not previously treated, without liver decompensation, and who are positive for serum HCV-RNA.
Rebetol huwa indikat għall- użu, f’ reġimen kombinat ma ’ interferon alfa- 2b, għall - kura ta ’ tfal u adolexxenti minn 3 snin ’ l fuq, li għandhom epatite C kronika, li ma kinux ikkurati qabel, mingħajr fwied mhux kompensat, u li huma pożittivi għall- HCV- RNA fis- serum.
The decision to treat should be made on a case by case basis, taking into account any evidence of disease progression such as hepatic inflammation and fibrosis, as well as prognostic factors for response, HCV genotype and viral load.
Id- deċiżjoni jekk għandhiex tingħata l- kura għandha tittieħed fuq bażi individwali skond il- każ, billi jitqies kull sinjal ta ’ avvanz tal- marda bħal infjammazzjoni epatika u fibrożi, kif ukoll fatturi ta ’ pronjożi għar- rispons, il- ġenotip HCV u l- viral- load.
The expected benefit of treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials (see sections 4.4, 4.8 and 5.1).
Il- benefiċċju mistenni mill- kura għandu jintiżen mas- sejbiet dwar is- sigurtà li jkunu jidhru f’ individwi pedjatriċi fil- provi kliniċi (ara sezzjonijiet 4. 4, 4. 8 u 5. 1).
Rebetol is indicated, in combination with interferon alfa-2b, for the treatment of adult patients with chronic hepatitis C who have previously responded (with normalisation of ALT at the end of treatment) to interferon alpha monotherapy but who have subsequently relapsed.
Pazjenti li jkunu fallew għall- kura li tkun ingħatat qabel Pazjenti adulti: Rebetol huwa indikat għall- użu, kombinat ma ’ interferon alfa- 2b, għall- kura ta ’ pazjenti adulti b’ epatite C kronika li qabel kienu wrew rispons (bin- normalizzazzjoni ta ’ l- ALT mat - tmiem tal- kura) għall- monoterapija ta ’ interferon alfa, iżda li wara rkadew.
Additionally, Rebetol is indicated, in combination with peginterferon alfa-2b, for the treatment of adult patients with chronic hepatitis C who have failed previous treatment with interferon alpha (pegylated or nonpegylated) and ribavirin combination therapy or interferon alpha monotherapy (see section 5.1).
2 kronika li fallew għall- kura li tkun ingħatat qabel b’ interferon alfa (pegilata jew mhux pegilata) u terapija kkombinata b’ ribavirin jew monoterapija b’ interferon alfa (ara sezzjoni 5. 1).
2 4.2 Posology and method of administration
4. 2 Pożoloġija u metodu ta ’ kif għandu jingħata
Treatment should be initiated, and monitored, by a physician experienced in the management of chronic hepatitis C.
It- terapija għandha tinbeda, u tkun monitorata, minn tabib li għandu esperjenza fl- immaniġġar ta ’ l - epatite C kronika.
Dose to be administered The dose of Rebetol is based on patient body weight (Table 1).
Doża li trid tingħata Id- doża ta ’ Rebetol hija bbażata fuq il- piż tal- ġisem tal- pazjent (Tabella 1).
Rebetol capsules are to be administered orally each day in two divided doses (morning and evening) with food.
Il- kapsuli ta ’ Rebetol għandhom jittieħdu mill- ħalq kuljum maqsumin f’ żewġ dożi (filgħodu u filgħaxija) ma ’ l- ikel.
Rebetol must be used in combination with either peginterferon alfa-2b (1.5 micrograms/ kg/ week) or interferon alfa-2b (3 million international units [MIU] three times a week).
Pazjenti adulti: Rebetol għandu jintuża flimkien ma ’ jew peginterferon alfa- 2b (1. 5 mikrogrammi/ kg/ ġimgħa) jew ma ’ interferon alfa- 2b (3 miljun unità internazzjonali [MIU] tliet darbiet fil- ġimgħa).
The choice of combination regimen is based on the characteristics of the patient.
L- għażla tar- reġimen kombinat hija bbażata fuq il- karatteristiċi tal- pazjent.
The regimen administered should be selected based on the anticipated efficacy and safety of the combination treatment for an individual patient (see section 5.1).
Ir - reġimen mogħti għandu jkun magħżul skond l- effikaċja u s- sigurtà mistennija mill- kura mħallta għall - pazjent individwali (ara sezzjoni 5. 1).
Table 1
Tabella 1:
Rebetol dose based on body weight
Numru ta ’ kapsuli ta ’ 200 mg 4a
1,200 mg 1,400 mg
1, 200 mg
2 morning, 3 evening c:
2 filgħodu, 3 filgħaxija c:
Rebetol Capsules in combination with pegylated interferon alfa-2b:
Rebetol Kapsuli kombinati ma ’ interferon alfa- 2b pegilat:
For patients who exhibit virological response at week 12, treatment should be continued for another nine month period (i. e., a total of 48 weeks).
Kemm għandha ddum il- kura – Pazjenti li qatt ma kienu ħadu din il- kura qabel Kemm jista ’ jkun imbassar ir- rispons viroloġiku sostnut: Pazjenti infettati b’ virus ġenotip 1 li ma jkollhomx rispons viroloġiku mat- 12- il ġimgħa x’ aktarx ma jiksbux rispons viroloġiku sostnut (ara wkoll sezzjoni 5. 1) • Ġenotip 1: Għal pazjenti li jiksbu rispons viroloġiku mat- 12- il ġimgħa, il- kura għandha titkompla għal perijodu ta ’ disa ’ xhur oħra (i. e. totali ta ’ 48 ġimgħa).
In the subset of patients with genotype 1 infection and low viral load (< 600,000 IU/ ml) who become HCV-RNA negative at treatment week 4 and remain HCV-RNA negative at week 24, the treatment could either be stopped after this 24 week treatment course or pursued for an additional 24 weeks (i. e. overall 48 weeks treatment duration).
Fis- sottogrupp ta’ pazjenti b’ ġenotip 1, infezzjoni u viral- load baxx (< 600, 000 IU/ ml) li jsiru negattivi għall- HCV- RNA mar- 4 ġimgħa ta ’ kura jibqgħu negattivi għal HCV- RNA mal- 24 ġimgħa, il- kura tista ’ jew titwaqqaf wara dan il- kors ta ’ 24 ġimgħa jew titkompla għal 24 ġimgħa oħra (i. e. b’ kollox 48 ġimgħa ta ’ kura).
In general, patients infected with genotype 4 are considered harder to treat and limited study data (n=66) indicate they are compatible with a duration of treatment as for genotype 1.
Madankollu, meta l- kura tingħata għal 24 ġimgħa jista ’ jkun riskju akbar li l- pazjent jirkadi milli meta jingħata kura ta ’ 48 ġimgħa (ara sezzjoni 5. 1). • Ġenotipi 2 jew 3: Huwa rrakkomandat li l- pazjenti kollha jkunu kkurati għal 24 ġimgħa, ħlief għall- pazjenti li jkollhom infezzjoni fl- istess ħin b’ HCV/ HIV li għandhom jieħdu kura ta ’ 48 ġimgħa. • Ġenotip 4: B’ mod ġenerali, pazjenti b’ ġenotip 4 huma meqjusa bħala aktar diffiċli biex tikkura u riżultat ta ’ studju limitat (n=66) jindika li jixraq li jkollhom tul ta ’ kura bħal dak ta ’ ġenotip 1.
HCV/ HIV Co-infection The recommended duration of dosing for HCV/ HIV co-infected patients is 48 weeks, regardless of genotype.
Infezzjoni fl- istess ħin b’ HCV/ HIV It- tul tad- dożaġġ irrakkomandat għall- pazjenti li jkollhom infezzjoni fl- istess ħin b’ HCV/ HIV huwa ta ’ 48 ġimgħa, ikun x’ ikun il- ġenotip.
Predictability of response and non-response in HCV/ HIV Co-infection Early virological response by Week 12, defined as a 2 log viral load decrease or undetectable levels of HCV-RNA, has been shown to be predictive for sustained response.
Kemm jista ’ jkun imbassar ir- rispons jew in- nuqqas tiegħu f’ infezzjonijiet fl- istess ħin b’ HCV/ HIV Rispons viroloġiku bikri ma ’ Ġimgħa 12, definit bħala 2 log tal- viral load jew livelli li ma jitkejlux ta ’ HCV- RNA, deher li setgħa jservi għat- tbassir ta ’ rispons sostnut.
The negative predictive value for sustained response in HCV/ HIV co-infected patients treated with Rebetol in combination with peginterferon alfa-2b was 99% (67/ 68; Study 1) (see section 5.1).
Valur ta ’ tbassir pożittiv ta ’ 50%
A positive predictive value of 50% (52/ 104; Study 1) was observed for HCV/ HIV co-infected patients receiving combination therapy.
3 (52/ 104; Studju 1) deher għal pazjenti infettati fl- istess ħin b’ HCV/ HIV li kienu qed jirċievu terapija kombinata.
3 Duration of treatment - Retreatment Predictability of sustained virological response:
Kemm għandha ddum il- kura – Trattament mill- ġdid Kemm jista ’ jiġi mbassar ir- rispons viroloġiku sostnut:
Retreated patients who fail to achieve virological response at Week 12 are unlikely to become sustained virological responders after 48 weeks of therapy (see also section 5.1).
Pazjenti kkurati mill- ġdid li ma jirnexxilhomx jiksbu rispons viroloġiku mat - 12- il Ġimgħa x’ aktarx li ma jiksbux rispons viroloġiku sostnut wara 48 ġimgħa ta ’ terapija (ara wkoll sezzjoni 5. 1).
Rebetol Capsules in combination with interferon alfa-2b:
Kapsuli Rebetol flimkien ma ’ interferon alfa- 2b:
Duration of treatment:
Kemm għandha ddum il- kura:
Based on the results of clinical trials, it is recommended that patients be treated for at least six months.
Fuq bażi tar- riżultati mill- provi kliniċi, huwa kkonsiljat li l- pazjenti jkunu kkurati għal mill- anqas sitt xhur.
During those clinical trials in which patients were treated for one year, patients who failed to show a virological response after six months of treatment (HCV-RNA below lower limit of detection) were unlikely to become sustained virological responders (HCV-RNA below lower limit of detection six months after withdrawal of treatment). • Genotype 1:
F’ dawk il- provi kliniċi fejn pazjenti kienu kkurati għal mill - anqas sena, pazjenti li ma wrewx rispons viroloġiku wara sitt xhur ta ’ kura (HCV- RNA taħt il- limitu baxx li jista ’ jitkejjel) kellhom anqas probabbiltà li jiksbu rispons viroloġiku sostnut (HCV- RNA taħt il- limitu baxx li jista ’ jitkejjel sitt xhur wara li twaqqfet il- kura). • Ġenotip 1:
The decision to extend therapy to one year in patients with negative HCV- RNA after six months of treatment should be based on other prognostic factors (e. g., age > 40 years, male gender, bridging fibrosis).
Il- kura għandha titkompla għal perijodu ieħor ta ’ sitt xhur (i. e., totali ta ’ sena) f’ pazjenti li jkollhom HCV- RNA negattiv wara sitt xhur ta ’ kura. • Ġenotipi li mhumhiex 1: Id- deċiżjoni sabiex il- kura tiġi estiża għal sena f’ pazjenti b’ HCV- RNA negattiv wara sitt xhur ta ’ kura għandha tkun ibbażata fuq fatturi ta ’ pronjożi oħrajn (eż età > 40 sena, sess maskili, fibrożi bridging).
Children aged three years and older, and adolescents:
Tfal ta ’ tlett snin u akbar, u adolexxenti:
(for patients who weigh < 47 kg, or are unable to swallow capsules, please refer to the SPC for ribavirin 40 mg/ ml oral solution).
(għal pazjenti li jiżnu < 47 kg, jew li ma jistgħux jibilgħu kapsuli, jekk jogħġbok irreferi għall- SPC ta ’ ribavirin 40 mg/ ml soluzzjoni orali).
In clinical studies performed in this population ribavirin and interferon alfa-2b were used in doses of 15 mg/ kg/ day and 3 MIU/ m2 three times a week respectively (Table 2).
Fi provi kliniċi li saru f’ din il- popolazzjoni ribavirin u interferon alfa- 2b intużaw f’ dożi ta ’ 15 mg/ kg/ jum u 3 MIU/ m2 tlett darbiet fil- ġimgħa rispettivament (Tabella 2).
Rebetol capsules are to be administered orally each day in two divided doses with food (morning and evening).
Il- kapsuli Rebetol għandhom jittieħdu mill- ħalq kuljum maqsumin f’ żewġ dożi ma ’ l- ikel (filgħodu u filgħaxija).
Rebetol paediatric dose based on body weight
Doża pedjatrika Rebetol skond il- piż
Number of 200 mg capsules 3 capsules a 4 capsules b
4 kapsuli b
Refer to adult dosing table (Table 1)
Irreferi għat- tabella ta ’ dużaġġi ta ’ l- adulti (Table 1)
1 morning, 2 b
2 filgħaxija
evening
b:
2 morning, 2
2 filgħodu, 2 filgħaxija
Duration of treatment in children and adolescents Genotype 1:
Kemm għandha ddum il- kura fi tfal u adolexxenti Ġenotip 1:
The recommended duration of treatment is 1 year.
Huwa irrakkomandat li l- kura għandha ddum sena 1.
Patients who fail to achieve virological response at 12 weeks are highly unlikely to become sustained virological responders (negative predictive value 96%).
Pazjenti li ma jkollhomx rispons viroloġiku mat- 12- il ġimgħa għandhom ferm anqas probabbiltà li jiksbu rispons viroloġiku sostnut (valur negattiv imbassar 96%).
Virological response is defined as absence of detectable HCV-RNA at Week 12 of treatment.
Rispons viroloġiku huwa definit bħala każ fejn HCV- RNA ma jkunx jista ’ jitkejjel mat- 12- il ġimgħa ta ’ kura.
Genotype 2 or 3:
Ġenotip 2 jew 3:
The recommended duration of treatment is 24 weeks.
Huwa irrakkomandat li l- kura għandha ddum għal 24 ġimgħa.
Virological responses after 1 year of treatment and 6 months of follow-up were 36% for genotype 1 and 81% for genotype 2/ 3/ 4.
Rispons viroloġiku wara sena 1 ta ’ kura u 6 xhur follow- up deher f’ 36% ta ’ dawk b’ ġenotip 1 u 81% ta ’ dawk b’ ġenotip 2/ 3/ 4.
Dose modification for all patients If severe adverse reactions or laboratory abnormalities develop during therapy with Rebetol and peginterferon alfa-2b or interferon alfa-2b, modify the dosages of each product if appropriate, until the adverse reactions abate.
Tibdil fid- doża għall- pazjenti kollha Jekk ikun hemm reazzjonijiet severi jew anormalitajiet fir- riżultati tal- laboratorju waqt it- terapija b’ Rebetol u peginterferon alfa- 2b jew interferon alfa- 2b, ibdel dawn id- dożaġġi ta ’ kull prodott jekk ikun xieraq, sakemm ir- reazzjonijiet avversi jbattu.
Guidelines were developed in clinical trials for dose modification (see Dosage modification guidelines, Table 3).
Saru linji gwida fi provi kliniċi għal tibdil fid- doża (ara Linji Gwida Għat- tibdil fid- Doża, Tabella 3).
The potential negative impact of ribavirin dose reduction on efficacy results could not be ruled out.
Minħabba li kemm il- pazjent jieħu l- kura kif suppost jista ’ jkun importanti għar- riżultat tat- terapija, id- doża għandha tinżamm kemm jista ’ jkun
4
4 qrib għad- doża rrakkomandata.
peginterferon alfa-2b
għall- modifikazzjoni fid- dożaġġ Naqqas id- doża ta ’ Naqqas id- doża ta ’
combination therapy
kuljum ta ’ Rebetol
600 mg/ day*,
600 mg/ jum *, u dik pedjatrika għall -
(adult) or interferon alfa-
alfa- 2b (adulti u pedjatriċi) biss
paediatric to 7.5 mg/ kg, if:
7. 5 mg/ kg jekk:
to one-half dose, if:
għal nofs id- doza, jekk:
Haemoglobin
Emoglobina Emoglobina adulta
in: patients with history of stable cardiac disease Paediatric: not applicable (see section 4.4)
f ’: pazjenti li
≥ 2 g/ dl 4
< 12 g/ dl wara
decrease in haemoglobin during any week period during treatment (permanent dose reduction)
perijodu ta ’ 4 ġimgħat waqt il- kura
< 12 g/ dl after 4 weeks of dose reduction
4 ġimgħat ta ’
White blood cells Neutrophils
(tnaqqis permanenti fid- doża)
- < 1.5 x 109/ l - < 0.75 x 109/ l
< 1. 5 x 109/ l -
< 1.0 x 109/ l < 0.5 x 109/ l
< 0. 5 x 109/ l
Adult < 50 x 109/ l
Adulti < 50 x 109/ l
Adult < 25 x 109/ l
Adulti < 25 x 109/ l
Paediatric < 80 x 109/ l
Pedjatriċi < 80 x 109/ l
Paediatric
Pedjatriċi
Bilirubin – Direct
Bilirubina – Diretta
2.5 x ULN**
2. 5 x ULN **
Bilirubin – Indirect
Bilirubina –
Adult > 4 mg/ dl
Adulti > 4 mg/ dl
Paediatric > 5 mg/ dl (for > 4 weeks)
Pedjatriċi > 5 mg/ dl (għal > 4 ġimgħat)
Alanine
Krejatinina Alanine Aminotransferase / apartate aminotransferase (ALT/ AST)
x baseline and
> 2. 0 mg/ dl 2 x linja bażi u > 10 x ULN **
Upper limit of normal
* Mogħtija billi tinqasam f’ żewġ dożi, filgħodu u filgħaxija ** Il- Limitu ta ’ Fuq tan- Normali
Use in renal impairment:
L- użu f’ pazjenti li jbatu minn indeboliment tal- kliewi:
The pharmacokinetics of ribavirin are altered in patients with renal dysfunction due to reduction of apparent clearance in these patients (see section 5.2).
Il- farmakokinetika ta ’ ribavirin tinbidel f’ pazjenti li għandhom il- kliewi mhux qed jaħdmu tajjeb minħabba li jidher tnaqqis ta ’ eliminazzjoni f’ dawn il- pazjenti (ara sezzjoni 5. 2).
Therefore, it is recommended that renal function be evaluated in all patients prior to initiation of Rebetol.
Għalhekk, huwa rrakkomandat li l- funzjoni tal- kliewi tkun imkejla fil- pazjenti kollha qabel jinbeda Rebetol.
Subjects with impaired renal function should be more carefully monitored with respect to the development of anaemia.
Pazjenti li għandhom rata tat- tneħħija mill- ġisem tal - krejatinina ta ’ < 50 ml/ minuta m’ għandhomx ikunu kkurati b’ Rebetol (ara sezzjoni 4. 3). Individwi li għandhom indeboliment fil- funzjoni renali għandhom ikunu monitorjati b’ aktar attenzjoni għal dak li għandu x’ jaqsam ma ’ l- anemija.
If serum creatinine rises to > 2 mg/ dl (Table 3), Rebetol and peginterferon alfa-2b/ interferon alfa-2b must be discontinued.
Jekk il- krejatinina fis- serum titla ’ għal > 2 mg/ dl (ara Tabella 3), Rebetol u peginterferon alfa- 2b/ interferon alfa- 2b għandhom jitwaqqfu.
Use in hepatic impairment:
L- użu f’ pazjenti li jbatu minn indeboliment tal- fwied:
No pharmacokinetic interaction appears between ribavirin and hepatic function (see section 5.2).
L- ebda azzjoni reċiproka farmakokinetika ma tidher bejn ribavirin u l- funzjoni tal- fwied (ara sezzjoni 5. 2).
Therefore, no dose adjustment of Rebetol is required in patients with hepatic impairment.
Għalhekk, l- ebda aġġustament fid- doża ta ’ Rebetol m’ huwa meħtieġ f’ pazjenti b’ indeboliment tal- fwied.
Use in the elderly (≥ 65 years of age):
5 Użu f’ pazjenti anzjani (Età ≥ 65 sena):
There does not appear to be a significant age-related effect on the pharmacokinetics of ribavirin.
Ma jidhirx li hemm xi effett sinifikanti konness ma ’ l- età fuq il- farmakokinetiċi ta ’ ribavirin.
However, as in younger patients, renal function must be determined prior to administration of Rebetol (see section 5.2).
Madankollu, bħal f’ pazjenti iżgħar, il- funzjoni tal- kliewi għandha tkun determinata qabel ma ’ Rebetol ikun mogħti (ara sezzjoni 5. 2).
Use in patients under the age of 18 years:
Użu f’ pazjenti li għandhom inqas minn 18- il sena:
Rebetol as capsules or oral solution may be used in combination with interferon alfa-2b in children (3 years of age and older) and adolescents.
Rebetol fil- forma ta ’ kapsuli jew soluzzjoni orali jista ’ jintuża flimkien ma ’ interferon alfa- 2b fi tfal (3 snin u akbar) u adolexxenti.
Safety and effectiveness of Rebetol with pegylated or other forms of interferon (i. e. not alfa-2b) in these patients have not been evaluated.
L- għażla dwar liema formulazzjoni tingħata tkun ibbażata fuq il- karatteristiċi individwali tal- pazjent (ara sezzjoni 4. 1). Is - sigurtà u l- effikaċja ta ’ Rebetol ma ’ interferon( i. e. mhux alfa- 2b) kemm dak pegilat kif ukoll forom oħra, f’ dawn il- pazjenti ma ġewx evalwati.
Patients co-infected with HCV/ HIV:
Pazjenti li fl- istess waqt ikollhom ukoll infezzjoni b’ HCV/ HIV:
Patients taking NRTI treatment in association with ribavirin and interferon alfa-2b or peginterferon alfa-2b may be at increased risk of mitochondrial toxicity, lactic 5 acidosis and hepatic decompensation (see section 4.4).
Pazjenti li qed jieħdu kura b’ NRTI flimkien ma ’ Ribavirin u interferon alfa- 2b jew peginterferon alfa- 2b jista ’ jkollhom riskju akbar ta ’ tossiċità mitokondrijali, aċidożi lattika u dikompensazzjoni epatika (ara sezzjoni 4. 4).
Please refer also to the relevant product information for antiretroviral medicinal products.
Jekk jogħġbok irreferi wkoll għat- tagħrif tal- prodott rilevanti għall- prodotti mediċinali antiretrovirali.
- Pregnant women (see sections 4.4, 4.6 and 5.3).
- Nisa waqt it- tqala (ara sezzjoni 4. 4, 4. 6 u 5. 3).
Rebetol must not be initiated until a report of a
Rebetol m’ għandux jinbeda qabel ma jinkiseb
negative pregnancy test has been obtained immediately prior to initiation of therapy.
rapport ta ’ riżultat negattiv għat- test tat- tqala eżatt qabel tinbeda t- terapija.
- Women who are breast-feeding.
- Nisa li qed ireddgħu.
- A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease,
- Meta ġa kien hemm mard kardijaku serju, li jinkludi mard kardijaku instabbli jew mhux
in the previous six months (see section 4.4).
kontrollat, fis- sitt xhur ta ’ qabel (ara sezzjoni 4. 4).
- Severe, debilitating medical conditions, including patients with chronic renal failure, patients
- Kondizzjonijiet mediċi severi u li jdgħajfu, li jinkludu pazjenti b’ insuffiċjenza kronika renali,
with creatinine clearance < 50 ml/ minute and/ or on haemodialysis.
b’ rata ta ’ < 50 ml/ minuta li biha titneħħa l- krejatinina u/ jew fuq magni tad- dijaliżi tad- demm.
- Severe hepatic dysfunction or decompensated cirrhosis of the liver.
- F’ każi severi fejn il- fwied ma jkunx qed jaħdem normali jew ċirrożi mhux ikkumpensata tal -
- Haemoglobinopathies (e. g., thalassemia, sickle-cell anaemia).
- Mard tad- demm (eż., talessimja, anemija tas- sickle cell)
- Initiation of peginterferon alfa-2b is contraindicated in HCV/ HIV patients with cirrhosis and a
- Huwa kontra- indikat li tinbeda kura bi peginterferon alfa- 2b f’ pazjenti HCV/ HIV b’ ċirrożi u
Child-Pugh score ≥ 6.
punteġġ Child- Pugh ≥ 6.
Children and adolescents:
Tfal u adolexxenti.
- Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal
- Jekk ikun hemm, jew xi darba kien hemm kundizzjoni psikjatrika severa, l- aktar f’ każ ta ’ dipressjoni
ideation, or suicide attempt.
severa, fissazzjoni ta ’ suwiċidju, jew tentattivi ta ’ suwiċidju.
Because of co-administration with peginterferon alfa-2b or interferon alfa-2b:
Minħabba l- għoti flimkien ta ’ peginterferon alfa- 2b jew interferon alfa- 2b:
- Autoimmune hepatitis; or history of autoimmune disease.
- Epatite awtoimmuni; jew jekk xi darba kien hemm mard awtoimmuni.
Psychiatric and Central Nervous System (CNS):
Psikjatriku u Sistema Nervuża Ċentrali (CNS):
Severe CNS effects, particularly depression, suicidal ideation and attempted suicide have been observed in some patients during Rebetol combination therapy with peginterferon alfa-2b or interferon alfa-2b, and even after treatment discontinuation mainly during the 6-month follow-up period.
Effetti severi tas- CNS, l- aktar dipressjoni, ħsibijiet ta ’ suwiċidju jew tentattivi ta ’ suwiċidju dehru f’ xi pazjenti waqt l- użu b’ terapija kombinata b’ Rebetol ma ’ peginterferon alfa- 2b jew interferon alfa- 2b, u anki wara li titwaqqaf il- kura u fil- perijodu ta ’ 6- xhur ta ’ wara.
Among children and adolescents, treated with Rebetol in combination with interferon alfa-2b, suicidal ideation or attempts were reported more frequently compared to adult patients (2.4% versus 1%) during treatment and during the 6-month follow-up after treatment.
Fost tfal u adolexxenti, kkurati b’ Rebetol kombinat ma ’ interferon alfa- 2b, każijiet ta ’ fissazzjoni jew tentattivi ta ’ suwiċidju kienu rrappurtati b’ mod aktar frekwenti milli f’ pazjenti adulti (2. 4% kontra 1%) waqt il- kura u waqt il- perijodu ta ’ 6- xhur ta ’ wara l- kura.
As in adult patients, children and adolescents experienced other psychiatric adverse events (e. g., depression, emotional lability, and somnolence).
Bħalma ġara f’ pazjenti adulti, tfal u adolexxenti kellhom effetti avversi psikjatriċi oħra (eż dipressjoni, burdati emozzjonali u ħedla).
Other CNS effects including aggressive behaviour (sometimes directed against others), confusion and alterations of mental status have been observed with alpha interferons.
Effetti CNS oħra li jinkludu atteġġjament aggressiv (xi drabi kontra individwi oħra), konfużjoni u tibdil fl- istat mentali dehru b’ alfa interferons.
Patients should be closely monitored for any signs or symptoms of psychiatric disorders.
Il- pazjenti għandhom ikunu monitorjati mill- qrib għal sinjali jew sintomi ta ’ mard psikjatriku.
If such symptoms appear, the potential seriousness of these undesirable effects must be borne in mind by the prescribing physician and the need for adequate therapeutic management should be considered.
Jekk jidhru dan it- tip ta ’ sintomi, it- tabib li qed jordna l- mediċini għandu jżomm f’ rasu kemm jistgħu jkunu serji dawn l- effetti mhux mixtieqa, u għandu jitqies il- bżonn għall- maniġġjar terapewtiku xieraq.
If psychiatric symptoms persist or worsen, or suicidal ideation is identified, it is recommended that treatment with Rebetol and peginterferon alfa-2b or interferon alfa-2b be discontinued, and the patient followed, with psychiatric intervention as appropriate.
Jekk sintomi psikjatriċi jippersistu jew imorru għall- agħar, jew jinstab li hemm fissazzjoni ta ’ suwiċidju, huwa rrakkomandat li l- kura b’ Rebetol u peginterferon alfa- 2b jew b’ interferon alfa- 2b titwaqqaf, u l- pazjent jibqa taħt osservazzjoni, u jkun hemm support psikjatriku xieraq.
If treatment with Rebetol in combination with peginterferon alfa-2b or interferon alfa-2b is judged necessary in adult patients with existence or history of severe psychiatric conditions, this should only be initiated after having ensured appropriate individualised diagnostic and therapeutic management of the psychiatric condition.
6 Pazjenti li jkollhom jew xi darba kellhom kundizzjonijiet psikjatriċi: Jekk ikun meqjus li meħtieġ tinbeda kura b’ Rebetol ma ’ peginterferon alfa- 2b jew interferon alfa- 2b f’ pazjenti adulti li jkollhom jew xi darba kellhom kundizzjonijiet psikjatriċi, din għandha tinbeda biss wara li jkun ġie żgurat li l - kundizzjoni psikjatrika ġiet dijanjostikata u kkontrollata b’ terapija xierqa għall- individwu.
The use of Rebetol and interferon alfa-2b in children and adolescents with existence of or history of severe psychiatric conditions is contraindicated (see section 4.3).
L- użu ta ’ Rebetol u interferon alfa- 2b fi tfal u adolexxenti li jkollhom jew xi darba kellhom kundizzjonijiet psikjatriċi severi huwa kontra- indikat (ara sezzjoni 4. 3)
Based on results of clinical trials, the use of ribavirin as monotherapy is not effective and Rebetol must not be used alone.
Skond ir- riżultati ta ’ studji kliniċi, l- użu ta ’ ribavirin bħala monoterapija mhuwiex effettiv u Rebetol m’ għandux jintuża waħdu.
The safety and efficacy of this combination have been established only using ribavirin capsules together with peginterferon alfa-2b or interferon alfa-2b solution for injection.
Is- sigurtà u l- effikaċja ta ’ din it- taħlita kienet stabbilita biss bl- użu tal - kapsuli ta ’ ribavirin flimkien mas- soluzzjoni għall- injezzjoni ta ’ peginterferon alfa- 2b jew interferon alfa - 2b.
All patients in the chronic hepatitis C studies had a liver biopsy before inclusion, but in certain cases (i. e. patients with genotype 2 and 3), treatment may be possible without histological confirmation.
Il- pazjenti kollha fl- istudji dwar l- epatite C kronika kellhom bijopsija tal- fwied qabel ma daħlu fl - istudju, imma f’ ċerti każijiet (i. e. pazjenti b’ ġenotip 2 u 3), il- kura tista ’ ssir mingħajr konfermazzjoni istoloġika.
6 Current treatment guidelines should be consulted as to whether a liver biopsy is needed prior to commencing treatment.
Il- linji gwida kurrenti tal- kura għandhom ikunu kkonsultati biex ikun stabbilit jekk il - bijopsija tal- fwied hijiex meħtieġa qabel ma tinbeda l- kura.
Teratogenic risk:
Riskju teratoġeniku:
Female patients:
Pazjenti nisa:
Rebetol must not be used by women who are pregnant (see section 4.3).
Rebetol m’ għandux jintuża minn nisa waqt it- tqala (ara sezzjoni 4. 3).
Extreme care must be taken to avoid pregnancy in female patients (see sections 4.6 and 5.3).
(ara sezzjonijiet 4. 6 u 5. 3).
Male patients and their female partners:
Pazjenti irġiel u s- sieħba femminili tagħhom:
Extreme care must be taken to avoid pregnancy in partners of male patients taking Rebetol (see sections 4.6 and 5.3).
Għandha tingħata attenzjoni kbira biex it- tqala tkun evitata fis- sieħba ta ’ pazjenti irġiel li jkunu qed jieħdu Rebetol (ara sezzjonijiet 4. 6 u 5. 3).
Haemolysis:
Emoliżi:
A decrease in haemoglobin levels to < 10 g/ dl was observed in up to 14% of adult patients and 7% of children and adolescents treated with Rebetol in combination with peginterferon alfa-2b (adults only) or interferon alfa-2b (adults and children or adolescents) in clinical trials.
Tnaqqis fil- livelli ta ’ l- emoglobina għal < 10 g/ dl kien osservat f’ sa 14% tal- pazjenti adulti u f’ 7% ta ’ tfal u adolexxenti kkurati b’ Rebetol flimkien ma ’ peginterferon alfa- 2b (adulti biss) jew interferon alfa- 2b (adulti u tfal jew adolexxenti) fi provi kliniċi.
Although ribavirin has no direct cardiovascular effects, anaemia associated with Rebetol may result in deterioration of cardiac function, or exacerbation of the symptoms of coronary disease, or both.
Għalkemm ribavirin m’ għandu l- ebda effetti kardjovaskulari diretti, anemija assoċjata ma ’ Rebetol tista ’ tirriżulta f’ deterjorament tal- funzjoni kardijaka, jew it- taħrix tas- sintomi ta ’ mard koronarju, jew it- tnejn.
Thus, Rebetol must be administered with caution to patients with pre-existing cardiac disease (see section 4.3).
Għalhekk, Rebetol għandu jkun mogħti b’ attenzjoni lill- pazjenti li ġa għandhom mard kardijaku (ara sezzjoni 4. 3).
Cardiac status must be assessed before start of therapy and monitored clinically during therapy; if any deterioration occurs, therapy must be stopped (see section 4.2).
L- istat kardijaku għandu jkun eżaminat qabel tinbeda t- terapija u osservat klinikament waqt it- terapija; jekk iseħħ xi deterjorament, it- terapija għandha titwaqqaf (ara sezzjoni 4. 2).
Cardiovascular:
Kardjovaskulari:
Adult patients with a history of congestive heart failure, myocardial infarction and/ or previous or current arrhythmic disorders must be closely monitored.
Pazjenti adulti li kellhom insuffiċjenza konġestiva tal- qalb, infart mijokardijaku, u/ jew irregolaritajiet fit- taħbit tal- qalb preżenti jew fil- passat, għandhom ikunu osservati mill- qrib.
It is recommended that those patients who have pre-existing cardiac abnormalities have electrocardiograms taken prior to and during the course of treatment.
Hu rrakkomandar li dawk il- pazjenti li għandhom anormalitajiet kardijaċi li kienu jeżistu minn qabel jittieħdu elettrokardjogrammi qabel u waqt il- kors tal- kura.
Cardiac arrhythmias (primarily supraventricular) usually respond to conventional therapy but may require discontinuation of therapy.
Arritmiji kardijaċi (primarjament supraventrikulari) normalment jirrispondu għat- terapija konvenzjonali imma għandhom mnejn ikollhom bżonn li titwaqqaf t- terapija.
There are no data in children or adolescents with a history of cardiac disease.
M’ hemmx tgħarif dwar tfal u adolexxenti li xi darba kellhom mard kardijaku.
If an acute hypersensitivity reaction (e. g., urticaria, angioedema, bronchoconstriction, anaphylaxis) develops, Rebetol must be discontinued immediately and appropriate medical therapy instituted.
Jekk tiżvillupa reazzjoni minħabba sensittività eċċessiva akuta (eż., urtikarja, anġoedema, jingħalqu l- bronki, anafilassi), Rebetol għandu jitwaqqaf minnufih u tinbeda terapija medika xierqa.
Transient rashes do not necessitate interruption of treatment.
F’ każijiet ta ’ raxx tal- ġilda momentarju m’ hemmx għalfejn titwaqqaf il- kura.
Ocular changes:
Tibdil fl- għajnejn:
Ribavirin is used in combination therapy with alpha interferons.
Ribavirin jintuża f’ kura flimkien ma ’ alfa 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 combination therapy with alpha interferons.
Retinopatija, inklużi emorraġiji retinali, dbabar bħal tajjar, papillo- edema, newropatija ottika u sadda ta ’ l- arterja jew vina tar- retina li tista ’ twassal għat- telf tal- vista kienu rrappurtati f’ xi każijiet b’ terapija kkombinata ma ’ alfa interferons.
All patients should have a baseline eye examination.
Il- pazjenti kollha għandu jkollhom eżami tal- għajnejn fil- bidu.
Any patient complaining of decrease or loss of vision must have a prompt and complete eye examination.
Kwalunkwe pazjent li jilmenta minn tnaqqis jew telf tal- vista għandu jiġi eżaminat bir- reqqa minnufih.
Combination therapy with alpha interferons should be discontinued in patients who develop new or worsening ophthalmologic disorders.
Pazjenti li jkollhom disturbi tal- għajnejn minn qabel (eż dijabete jew retinopatija ta ’ sensittività eċċessiva) għandu jkollhom eżamijiet tal- għajnejn waqt terapija kkombinata b’ alfa interferons. it- terapija kkombinata b’ alfa interferons għandha titwaqqaf f’ pazjenti li jkollhom disturbi ġodda tal- għajnejn jew li jaggravaw.
Liver function:
7 Funzjoni tal- fwied:
Any patient developing significant liver function abnormalities during treatment must be monitored closely.
Kwalunkwe pazjent li jiżviluppa anormalitajiet sinifikanti fil- funzjoni tal- fwied waqt il- kura għandu jkun osservat mill- qrib.
Discontinue treatment in patients who develop prolongation of coagulation markers which might indicate liver decompensation.
Waqqaf il- kura f’ dawk il- pazjenti li jkollhom dewmien fil- markers tal- koagulazzjoni tad- demm li jista ’ jindika nuqqas ta ’ kumpens tal- fwied.
Supplemental monitoring specific for children and adolescents
Monitoraġġ supplimentari speċifiku għat- tfal u adolexxenti
During a 1-year course of therapy there was a decrease in the rate of linear growth (mean percentile decrease of 9%) and a decrease in the rate of weight gain (mean percentile decrease of 13%).
Waqt kors ta ’ terapija ta ’ sena kien hemm tnaqqis fir- rata ta ’ tkabbir lineari (perċentwal medju ta ’ tnaqqis ta ’ 9%) u tnaqqis fir- rata ta ’ żieda fil- πiż tal- ġisem (perċentwal medju ta ’ tnaqqis ta ’ 13%).
A general reversal of these trends was noted during the 6 months follow-up post treatment.
Fil- perijodu ta ’ 6 xhur ta ’ wara li twaqqfet il- kura kienu reġistrati tendenzi ġenerali li jieqfu jikbru.
However, based on interim data from a long-term follow-up study, 12 (14%) of 84 children had a > 15 percentile decrease in rate of linear growth, of whom 5 (6%) children had a > 30 percentile decrease despite being off treatment for more than 1 year.
Madankollu, minn tgħarif li nġabar filwaqt li kien qed isir studju follow up fit - tul, 12 (14%) minn 84 tifel u tifla kellhom > 15% perċentwali ta ’ tnaqqis fir- rata ta ’ żieda fit- tul, li minnhom, 5t itfal (6%) kellhom > 30 perċentwali ta ’ tnaqqis minkejja li kienu ilhom aktar minn sena li waqfu mill- kura.
In addition, preclinical juvenile toxicity results have demonstrated a minor, dose-related decrease in overall growth in neonatal rats dosed with ribavirin (see section 5.3).
Minbarra hekk, riżultati ta ’ tossiċità fiż- żagħżagħ qabel l- użu kliniku wrew tnaqqis żgħir, marbut mad- doża fil- mod ġenerali kif kibru firien tat- twelid li ngħataw dożi b’ ribavirin (ara sezzjoni 5. 3).
Therefore, the risk/ benefit of the combined use of Rebetol and interferon alfa-2b should be assessed in young children prior to the initiation of therapy.
Għaldaqstant għandu jitqies ir- riskju/ benefiċċju ta ’ l- użu kombinat ta ’ Rebetol ma ’ interferon alfa- 2b fi tfal żgħar qabel ma tinbeda t- terapija.
Physicians are advised to monitor the growth of children taking Rebetol in combination with interferon alfa-2b.
It- tobba huma kkunsiljati li jsegwu l- mod kif ikunu qed jikbru tfal li jkunu qed jieħdu Rebetol kombinat ma ’ interferon alfa- 2b.
There are no data on long term effects on growth and development and on sexual maturation.
M’ hemmx tgħarif dwar l- effetti li jkun hemm bl- użu fit- tul fuq it- tkabbir u żvilupp sesswali.
7 Thyroid Monitoring:
Monitoraġġ tat- tirojde:
Approximately 12% of children treated with Rebetol and interferon alfa-2b developed increase in TSH.
Madwar 12% tat- tfal ikkurati b’ Rebetol u interferon alfa- 2b żviluppaw żieda fit- TSH.
Another 4% had a transient decrease below the lower limit of normal.
4% oħra kellhom tnaqqis momentanju taħt l- aktar limitu baxx tan- normali.
Prior to initiation of interferon alfa-2b therapy, TSH levels must be evaluated and any thyroid abnormality detected at that time must be treated with conventional therapy.
Qabel ma tinbeda terapija b’ interferon alfa- 2b, il- livelli ta ’ TSH għandhom jitqiesu u kwalunkwe anormalitàjiet fit - tirojdi li jinstabu f’ dak il- ħin għandhom ikunu kkurati b’ terapiji konvenzjonali.
Interferon alfa-2b therapy may be initiated if TSH levels can be maintained in the normal range by medication.
It- terapija b’ interferon alfa- 2b tista ’ tinbeda jekk il- livelli ta ’ TSH ikunu jistgħu jinżammu fil- medda normali permezz ta ’ medikazzjoni.
Thyroid dysfunction during treatment with Rebetol and interferon alfa-2b has been observed.
Funzjoni ħażina tat- tirojdi waqt il- kura b’ Rebetol u interferon alfa- 2b kienet innutata.
If thyroid abnormalities are detected, the patient ’ s thyroid status should be evaluated and treated as clinically appropriate.
Jekk jinstabu anormalitajiet tat- tirojdi, l- istat tat- tirojdi tal- pazjent għandu jitqies u jiġi kkurat kif ikun klinikament xieraq.
TSH).
It- tfal u l- adolexxenti għandhom ikunu monitorjati kull 3 xhur għal sinjali li jistgħu juru funzjoni ħażina tat- tirojdi (eż TSH).
Mitochondrial toxicity and lactic acidosis:
Infezzjoni fl- istess ħin b’ HCV/ HIV Tossiċità mitokondrijali u aċidożi lattika:
Caution should be taken in HIV-positive subjects co-infected with HCV who receive nucleoside reverse transcriptase inhibitor (NRTI) treatment (especially ddI and d4T) and associated interferon alfa-2b/ ribavirin treatment.
Għandha tingħata attenzjoni lill- pazjenti pożittivi għall- HIV li huma ko- infettati bl- HCV li qed jirċievu kura bl- impedituri ta ’ nucleoside reverse transcriptase (NRTI) (l- aktar ddI u d4T) u l- kura assoċjata interferon alfa- 2b/ ribavirin.
In the HIV-positive population receiving an NRTI regimen, physicians should carefully monitor markers of mitochondrial toxicity and lactic acidosis when ribavirin is administered.
Fil- popolazzjoni pożittiva għall- HIV li qed jirċievu reġimen b’ NRTI, it- tobba għandhom josservaw b’ attenzjoni il- markers tat- tossiċità mitokondrijali u aċidożi lattika meta jingħata ribavirin.
In particular:
L- aktar:
- co-administration of Rebetol and didanosine is not recommended due to the risk of
- l- użu ta ’ Rebetol flimkien ma ’ didanosine mhuwiex irrakkomandat minħabba riskju ta ’ tossiċità
mitochondrial toxicity (see section 4.5).
mitokondrijali (ara sezzjoni 4. 5).
- co-administration of Rebetol and stavudine should be avoided to limit the risk of overlapping
- l- użu ta ’ Rebetol ma ’ stavudine għandu jiġi evitat sabiex ir- riskju ta ’ tossiċità mitokondrijali miż -
mitochondrial toxicity.
żewġ mediċini f’ daqqa jkun limitat.
Hepatic decompensation in HCV/ HIV co-infected patients with advanced cirrhosis:
Pazjenti nfettati fl- istess ħin HCV/ HIV li jkollhom ċirrożi fi stat avvanzat:
Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic decompensation and death.
Pazjenti infettati fl- istess ħin li jkollhom ċirrożi avanzata u li jkunu qed jirċievu HAART jista ’ jkollhom riskju akbar ta ’ dikumpens epatiku u mewt.
Adding treatment with alfa interferons alone or in combination with ribavirin may increase the risk in this patient subset.
Iż- żieda ta ’ trattament b’ interferoni alfa waħdu jew f’ taħlita ma ’ ribavirin jista ’ jżid ir- riskju f’ dan is- sottogrupp ta ’ pazjenti.
Other baseline factors in co-infected patients that may be associated with a higher risk of hepatic decompensation include treatment with didanosine and elevated bilirubin serum concentrations.
Fatturi mal- linja bażi oħrajn f’ pazjenti infettati fl- istess ħin li jistgħu jkunu assoċjati ma ’ riskju akbar ta ’ dikumpens epatiku jinkludu kura b’ didanosine u livell għoli ta ’ bilirubin fis- serum.
Co-infected patients receiving both antiretroviral (ARV) and anti-hepatitis treatment should be closely monitored, assessing their Child-Pugh score during treatment.
Pazjentiinfettati fl- istess ħin li qed jirċievu kemm kura antiretrovirali (ARV) kif ukoll kura kontra l - epatite għandhom ikunu monitorjati mill- qrib, tiġi kkalkulata l- iskala Child- Pugh tagħhom waqt il - kura.
Patients progressing to hepatic decompensation should have their anti-hepatitis treatment immediately discontinued and the ARV treatment reassessed.
Pazjenti li javanzaw għal nuqqas ta ’ kumpens epatiku għandu jkollhom il- kura tagħhom kontra l - epatite mwaqqfa mill- ewwel u l- kura ARV terġa tiġi evalwata mill- ġdid.
Haematological abnormalities in HCV/ HIV co-infected patients:
Anormalitajiet ematoloġiċi f’ pazjenti li jkollhom fl- istess ħin HCV/ HIV:
HCV/ HIV co-infected patients receiving peginterferon alfa-2b/ ribavirin treatment and HAART may be at increased risk to develop haematological abnormalities (as neutropenia, thrombocytopenia and anaemia) compared to HCV mono-infected patients.
Għalkemm
Although, the majority of them could be managed by dose reduction, close monitoring of haematological parameters should be undertaken in this population of patients (see section 4.2 and below “ Laboratory tests” and section 4.8).
8 il- biċċa l- kbira jistgħu jkunu mmaniġġjati bi tnaqqis fid- doża, monitoraġġ mill- qrib ta ’ parametri ematoloġiċi għandu jsir f’ dan il- grupp ta ’ pazjenti (ara sezzjonijiet 4. 2 u hawn taħt “ Testijiet tal - Laboratorju ” u sezzjoni 4. 8).
Patients treated with ribavirin and zidovudine are at increased risk of developing anaemia; therefore, the concomitant use of ribavirin with zidovudine is not recommended (see section 4.5).
Pazjenti kkurati b’ ribavirin u zidovudine għandhom riskju akbar li jiżviluppaw anemija, għalhekk, l - użu ta ’ ribavirin flimkien ma ’ zidovudine mhux irrakkomandat (ara sezzjoni 4. 5).
In patients co-infected with HCV/ HIV, limited efficacy and safety data (N = 25) are available in subjects with CD4 counts less than 200 cells/ µl.
F’ pazjenti li jkollhom fl- istess ħin HCV/ HIV, dejta limitata dwar l- effikaċja u s- sigurtà (N=25) huma disponibbli f’ individwi b’ għadd tas- CD4 anqas minn 200 cellula/ µl.
Caution is therefore warranted in the treatment of patients with low CD4 counts.
Għalhekk wieħed għandu joqgħod attent meta jkunu qed jiġu kkurati pazjenti b’ għadd tas- CD4 baxx.
Please refer to the respective Summary of Product Characteristics of the antiretroviral medicinal products that are to be taken concurrently with HCV therapy for awareness and management of toxicities specific for each product and the potential for overlapping toxicities with Rebetol and peginterferon alfa-2b.
Jekk jogħġbok irreferi għas- Sommarju tal- Karatteristiċi tal- Prodott tal- prodotti mediċinali antiretrovirali li jkollhom jittieħdu fl- istess ħin ma ’ terapija HCV għall- għarfien u maniġġjar tat - tossiċitajiet speċifiċi għal kull prodott u l- potenzjal li jista ’ jkun hemm tossiċitajiet f ’ daqqa b ’ Rebetol u peginterferon alfa- 2b.
Dental and periodontal disorders:
Mard tas- snien u tal- ħalq:
In addition, dry mouth could have a damaging effect on teeth and mucous
Mard tas- snien u tal- ħalq li minħabba fihom jistgħu jaqgħu is- snien, kienu rrappurtati f’ pazjenti li kienu qed jieħdu terapija kombinata b’ Rebetol u peginterferon alfa- 2b jew interferon alfa- 2b.
8 membranes of the mouth during long-term treatment with the combination of Rebetol and peginterferon alfa-2b or interferon alfa-2b.
Minbarra hekk, ħalq xott jista ’ jgħamel ħsara lis- snien u ’ l- membrani tal- mukoża fil- ħalq waqt kura kombinata fit- tul b’ Rebetol u peginterferon alfa- 2b jew interferon alfa- 2b.
Patients should brush their teeth thoroughly twice daily and have regular dental examinations.
Il - pazjenti għandhom jaħslu snienhom sew darbtejn kuljum u jkollhom snienhom eżaminati b’ mod regolari.
In addition some patients may experience vomiting.
Minbarra hekk, xi pazjenti jistgħu jirrimettu.
If this reaction occurs, they should be advised to rinse out their mouth thoroughly afterwards.
Jekk jiġri hekk, għandhom jaħslu ħalqhom wara.
Standard haematologic tests and blood chemistries (complete blood count [CBC] and differential, platelet count, electrolytes, serum creatinine, liver function tests, uric acid) must be conducted in all patients prior to initiating therapy.
Qabel ma tinbeda t- terapija fil- pazjenti kollha għandhom isiru testijiet tad- demm kemm dawk standard kif ukoll kimiċi (għadd komplet tad- demm [CBC] u differenzjali, l- għadd tal - plejtlets, elettroliti, krejatinina fis- serum, testijiet tal- funzjoni tal- fwied, uric acid).
Acceptable baseline values that may be considered as a guideline prior to initiation of Rebetol therapy:
Valuri aċċettabbli tal- linja bażi li jistgħu jitqiesu bħala linji gwida qabel tinbeda t- terapija b’ Rebetol:
Adult: ≥ 12 g/dl (females); ≥ 13 g/dl (males) Paediatric: ≥ 11 g/dl (females); ≥ 12 g/dl (males)
• Adulti: ≥ 12 g/ dl (nisa); ≥ 13 g/ dl (irġiel) Emoglobina Pedjatriċi: ≥ 11 g/ dl (nisa); ≥ 12 g/ dl (irġiel) ≥ 100, 000/ mm3 • Plejtlets ≥ 1, 500/ mm3 • Għadd tan- Newtrofili
Laboratory evaluations are to be conducted at weeks 2 and 4 of therapy, and periodically thereafter as clinically appropriate.
Evalwazzjonijiet tal- laboratorju għandhom isiru fit- 2 u fir- 4 ġimgħa tat- terapija, u kultant żmien wara dan, kif ikun klinikament xieraq.
For females of childbearing potential:
Għal nisa li jista ’ jkollhom it- tfal:
Female patients must have a routine pregnancy test performed monthly during treatment and for four months thereafter.
Pazjenti nisa għandu jkollhom testijiet tat- tqala ta ’ rutina kull xahar waqt il- kura u għal erba ’ xhur wara.
Female partners of male patients must have a routine pregnancy test performed monthly during treatment and for seven months thereafter (see section 4.6).
Is- sieħba nisa ta ’ pazjenti rġiel għandu jkollhom testijiet tat- tqala ta ’ rutina kull xahar waqt il- kura u għal seba ’ xhur wara (ara sezzjoni 4. 6).
Uric acid may increase with Rebetol due to haemolysis; therefore, the potential for development of gout must be carefully monitored in pre-disposed patients.
Uric acid għandu mnejn jiżdied b’ Rebetol minħabba ħemoliżi; għalhekk, il- potenzjal għall- iżvilupp ta ’ gotta għandu jkun osservat b’ attenzjoni f’ pazjenti predisposti.
Use in patients with rare hereditary disorders:
L- użu f’ pazjenti b’ mard ereditarju rari:
Each Rebetol capsule contains 40 mg of lactose.
Kull kapsula fiha 40 mg lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Pazjenti bi problemi ereditarji rari ta ’ intolleranza għal galactose, id- defiċjenza ta ’ Lapp Lactase jew assorbiment ħażin ta ’ glucose / galactose m’ għandhomx jieħdu din il- mediċina.
Results of in vitro studies using both human and rat liver microsome preparations indicated no cytochrome P450 enzyme mediated metabolism of ribavirin.
Ir- riżultati ta ’ studji in vitro li użaw preparazzjonijiet ta ’ mikrożomi tal- fwied kemm umani kif ukoll tal- firien ma ’ indikaw l- ebda metaboliżmu ta ’ ribavirin medjat mill- enżima tas- cytochrome P450.
Ribavirin does not inhibit cytochrome P450 enzymes.
Ribavirin ma timpedixxix l- enżimi tas- cytochrome P450.
There is no evidence from toxicity studies that ribavirin induces liver enzymes.
M’ hemm l- ebda evidenza minn studji dwar it - tossiċità li ribavirin jinduċi l- enżimi tal- fwied.
Therefore, there is a minimal potential for P450 enzyme-based interactions.
Għalhekk, hemm probabbilta ’ minima li jseħħu interazzjonijiet bażati fuq l- enzima P450.
No interaction studies have been conducted with Rebetol and other medicinal products, except for peginterferon alfa-2b, interferon alfa-2b and antacids.
9 Ma saru l- ebda studji dwar l- interazzjoni bejn Rebetol u prodotti mediċinali oħra, ħlief għall - peginterferon alfa- 2b, interferon alfa- 2b u mediċini kontra l- aċidu fl- istonku.