qanastek/EMEA-V3 huggingface dataset:
HBeAg negative (study 027): treatment with entecavir up to 96 weeks (n = 325) resulted in cumulative response rates of 94% for HBV DNA < 300 copies/ ml by PCR and 89% for ALT normalisation versus 77% for HBV DNA < 300 copies/ ml by PCR and 84% for ALT normalisation for lamivudine-treated patients (n = 313).
Negattivi għal HBeAg (studju 027): trattament b’ entecavir sa 96 ġimgħa (n= 354) irriżulta f’ rati ta ’ titjib kumulattiv ta ’ 94% għal DNA ta ’ HBV < 300 kopja/ ml skond il- PCR u 89% għal normalizzazzjoni ta ’ l- ALT meta mqabbel ma ’ 77% għal DNA ta ’ HBV < 300 kopja/ ml skond il- PCR u 84% għal normalizzazzjoni ta ’ l- ALT f’ pazjenti ttrattati b’ lamivudine (n= 313).
For 26 entecavir-treated and 28 lamivudine-treated patients who continued treatment beyond 52 weeks (median 96 weeks), 96% of entecavir-treated and 64% of lamivudine-treated patients had HBV DNA < 300 copies/ ml by PCR at end of dosing.
Għal 26 pazjent li ġew ittrattati b’ entecavir u 28 pazjent li ġew ittrattati għal iktar minn 52 ġimgħa (medja ta ’ 96 ġimgħa), 96% ta ’ dawk il- pazjenti ittrattati b’ entecavir u 64% ta ’ dawk il- pazjenti ttrattati b’ lamivudine kellhom DNA ta ’ HBV < 300 kopja/ ml skond il- PCR fl- aħħar tad- dożi.
ALT normalisation (≤ 1 times ULN) occurred in 27% of entecavir-treated and 21% of lamivudine-treated patients at end of dosing.
In - normalizzazzjoni ta ’ l- ALT (≤ 1 x ULN) instabet f’ 27% tal- pazjenti ttrattati b’ entecavir u f’ 21% tal - pazjenti ttrattati b’ lamivudine fl- aħħar tad- dożi.
For patients who met protocol-defined response criteria, response was sustained throughout the 24-week post-treatment follow-up in 75% (83/ 111) of entecavir responders vs 73% (68/ 93) for lamivudine responders in study 022 and 46% (131/ 286) of entecavir responders vs 31% (79/ 253) for lamivudine responders in study 027.
10 Għal pazjenti li ssodisfaw il- kriterji li ġew definiti fi protokoll, it- titjib kompla matul il- follow- up ta ’ 24 ġimgħa wara t- trattament f’ 75% (83/ 111) tal- pazjenti li rrispondew għal entecavir kontra 73% (68/ 93) għal dawk li rrispondew għal lamivudine fi studju 022 u 46% (131/ 286) ta ’ dawk li rrispondew għal entecavir meta mqabbel ma ’ 31% (79/ 253) għal pazjenti li rrispondew għal lamivudine fi studju 027.
By 48 weeks of post-treatment follow-up, a substantial number of HBeAg negative patients lost response.
Wara 48 ġimgħa ta ’ follow- up wara t- trattament, numru sustanzjali ta ’ pazjenti negattivi għal HbeAg irkadew.
Lamivudine-refractory:
Rifrattorji għal Lamivudine:
HBeAg positive (study 026): treatment with entecavir for up to 96 weeks (n = 141) resulted in cumulative response rates of 30% for HBV DNA < 300 copies/ ml by PCR, 85% for ALT normalisation and 17% for HBeAg seroconversion.
Pożittivi għal HBeAg (studju 026): trattament b’ entecavir sa 96 ġimgħa (n= 141) irriżulta f’ rati ta ’ titjib kumulattiv ta ’ 30% għal DNA ta ’ HBV < 300 kopja/ ml skond il- PCR, 85% għal normalizzazzjoni ta ’ l- ALT u 17% għal sirokonversjoni ta ’ l- HBeAg.
For the 77 patients who continued entecavir treatment beyond 52 weeks (median 96 weeks), 40% of patients had HBV DNA < 300 copies/ ml by PCR and 81% had ALT normalisation (≤ 1 times ULN) at end of dosing.
Għas- 77 pazjent li komplew it- trattament b’ entecavir għal iktar min 52 ġimgħa (medja ta ’ 96 ġimgħa), 40% tal- pazjenti kellhom DNA ta ’ HBV < 300 kopja/ ml skond il- PCR waqt li normalizzazzjoni ta ’ l - ALT (≤ 1 x ULN) instabet f’ 81% tal- pazjenti fl- aħħar tad- dożi.
Age/ gender:
Età/ ġeneru:
There was no apparent difference in efficacy for entecavir based on gender (≈ 25% women in the clinical trials) or age (≈ 5% of patients > 65 years of age).
Ma tfaċċat l- ebda differenza fl- effikaċja ta ’ entecavir fuq il- bażi tal- ġeneru (≈ 25% tan- nisa fi provi kliniċi) jew età (≈5% tal- pazjenti > 65 sena).
Special populations HIV/ HBV co-infected patients receiving concomitant HAART: study 038 included 67 HBeAg positive and 1 HBeAg negative patients co-infected with HIV.
Gruppi speċjali Pazjenti ko- infettati bl- HIV/ HBV li jkunu qed jingħataw HAART fl- istess ħin: fl- istudju 038 kien hemm 67 pazjent pożittiv għal HBeAg u pazjent wieħed negattiv għal HBeAg li kienu infettati wkoll bl- HIV.
Patients had stable controlled HIV (HIV RNA < 400 copies/ ml) with recurrence of HBV viraemia on a lamivudine-containing HAART regimen.
Il- pazjenti kellhom HIV stabbli u kkontrollata (HIV RNA < 400 kopji/ ml) b’ rikorrenza tal - viremja ta ’ l- HBV fuq reġimen b’ lamivudine bħala parti mit- terapija HAART.
HAART regimens did not include emtricitabine or tenofovir disoproxil fumarate.
Ir- reġimen ta ’ HAART ma nkludewx emtricitabine jew tenofovir disoproxil fumarate.
At baseline entecavir-treated patients had a median duration of prior lamivudine therapy of 4.8 years and median CD4 count of 494 cells/ mm3 (with only 5 subjects having CD4 count < 200 cells/ mm3).
Fil- linja bażi, pazjenti ttrattati b’ entecavir kellhom terapija preċedenti b’ lamivudine għal medja ta ’ 4. 8 snin u ammont medju ta ’ CD4 ta ’ 494 ċelloli/ mm3 (b’ 5 pazjenti biss li kellhom ammont ta ’ CD4 < 200 ċellola/ mm3).
Patients continued their lamivudine-regimen and were assigned to add either entecavir 1 mg once daily (n = 51) or placebo (n = 17) for 24 weeks followed by an additional 24 weeks where all received entecavir.
Il- pazjenti komplew il- programm tagħhom ta ’ lamivudine u ġew assenjati biex iżidu jew 1 mg ta ’ entecavir darba kuljum (n= 51) jew plaċebo (n= 17) għal 24 ġimgħa u dan tkompla b’ 24 ġimgħa oħra fejn kollha rċevew entecavir.
At 24 weeks the reduction in HBV viral load was significantly greater with entecavir (-3.65 vs an increase of 0.11 log10 copies/ ml).
Fl- 24 ġimgħa, it- tnaqqis fil- viral load ta ’ l- HBV kien ferm ogħla b’ entecavir (- 3. 65 meta mqabbel ma ’ żjieda ta ’ 0. 11 log10 kopji/ ml).
For patients originally assigned to entecavir treatment, the reduction in HBV DNA at 48 weeks was -4.20 log10 copies/ ml, ALT normalisation had occurred in 37% of patients with abnormal baseline ALT and none achieved HBeAg seroconversion.
Għal pazjenti li oriġinarjament ġew assenjati għal trattament b’ entecavir, it- tnaqqis fid- DNA ta ’ HBV wara 48 ġimgħa kien - 4. 8 log10 kopji/ ml, normalizzazzjoni ta ’ l- ALT seħħet f’ 37% tal- pazjenti b’ ALT ta ’ linja bażi anormali u ħadd minnhom ma ’ laħaq sirokonversjoni ta ’ HBeAG.
10 HIV/ HBV co-infected patients not receiving concomitant HAART: entecavir has not been evaluated in HIV/ HBV co-infected patients not concurrently receiving effective HIV treatment.
Pazjenti ko- infettati bl- HIV/ HBV li ma jkunux qed jingħataw HAART fl- istess ħin: entecavir ma ġiex evalwat f’ pazjenti infettati fl- istess ħin bl- HIV/ HBV li ma kinux qegħdin jirċievu fl- istess ħin kura effettiva kontra l- HIV.
Reductions in HIV RNA have been reported in HIV/ HBV co-infected patients receiving entecavir monotherapy without HAART.
Ġie rrapportat tnaqqis fl- HIV RNA f’ pazjenti infettati fl- istess ħin bl- HIV/ HBV li kienu qegħdin jingħataw monoterapija b’ entecavir mingħajr HAART.
In some cases, selection of HIV variant M184V has been observed, which has implications for the selection of HAART regimens that the patient may take in the future.
F’ xi każijiet, kienet osservata għażla tal- varjant ta ’ l- HIV M184V, u dan għandu implikazzjonijiet għall- għażla tar- reġimen ta ’ HAART li l- pazjent jista ’ jieħu fil- futur.
Therefore, entecavir should not be used in this setting due to the potential for development of HIV resistance (see section 4.4).
Għalhekk, entecavir m’ għandux jintuża f’ dawn iċ- ċirkustanzi minħabba l- potenzjal għall- iżvilupp ta ’ reżistenza ta ’ l- HIV (ara sezzjoni 4. 4).
Patients with decompensated liver disease: a randomised open-label study (048) comparing entecavir 1.0 mg once daily with adefovir 10 mg once daily in patients with hepatic decompensation is ongoing.
Pazjenti b’ mard tal- fwied di- kumpensat: hemm studju b’ mod każwali, open- label (048) għaddej li jqabbel 1. 0 mg ta ’ entecavir darba kuljum ma ’ 10 mg ta ’ adefovir darba kuljum f’ pazjenti b’ di - kumpensazzjoni tal- fwied.
Clinical resistance: patients in clinical trials initially treated with entecavir 0.5 mg (nucleoside-naive) or 1.0 mg (lamivudine-refractory) and with an on-therapy PCR HBV DNA measurement at or after Week 24 were monitored for resistance.
Reżistenza klinika: il- pazjenti fil- provi kliniċi inizjalment ittrattati b’ entecavir 0. 5 mg (nucleoside - naive) jew 1. 0 mg (lamivudine- rifrattorji) u b’ kejl tal- PCR HBV DNA waqt it- terapija f’ Ġimgħa 24 jew wara ġew immonitorjati għar- reżistenza.
Through Week 240 in nucleoside-naive studies, genotypic evidence of ETVr substitutions at rtT184, rtS202, or rtM250 was identified in 3 patients treated with entecavir, 2 of whom experienced virologic breakthrough (see table).
Sa Ġimgħa 240 fi studji dwar pazjenti li qatt ma ħadu nukleoside, evidenza ġenotipika ta ’ sostituzzjonijiet ETVr f’ rtT184, rtS202, jew rtM250 kienet identifikati fi 3 pazjenti kkurati b’ entecavir, u 2 minnhom kellhom breakthrough viroloġiku (ara t- tabella).
These substitutions were observed only in the presence of LVDr substitutions (rtM204V and rtL180M).
Dawn is- sostituzzjonijiet kienu osservati biss fil- preżenza ta ’ sostituzzjonijiet LVDr (rtM204V u rtL180M).
Emerging Genotypic Entecavir Resistance Through Year 5, Nucleoside-Naive Studies a
11 Reżistenza Ġenotipika Ġdida għal Entecavir Sa Sena 5, Studji dwar Pazjenti li Qatt ma Ħadu Nukleoside a
Year 1
Sena 1
Year 2
Sena 2
Year 3
Sena 3
Patients treated and monitored for b resistance Patients in specific year with:
Pazjenti kkurati u mmonitorjati għal - b reżistenza Pazjenti f’ sena speċifika b ’:
c - emerging genotypic ETVr
c - ETVr ġenotipika ġdida
c - genotypic ETVr with virologic d breakthrough Cumulative probability of:
c - ETVr ġenotipika bi d breakthrough viroloġika Probabbiltà kumuluttiva ta ’:
- emerging genotypic ETVr
c - ETVr ġenotipika ġdida
c - genotypic ETVr with virologic d breakthrough a
c - ETVr ġenotipika bi d breakthrough viroloġika a
Results reflect use of a 1-mg dose of entecavir for 147 of 149 patients in Year 3 and all patients in Years 4 and 5 and of combination entecavir-lamivudine therapy (followed by long-term entecavir therapy) for a median of 20 weeks for 130 of 149 patients in Year 3 and for 1 week for 1 of 121 patients in Year 4 in a rollover study. b Includes patients with at least one on-therapy HBV DNA measurement by PCR at or after week 24 through week 58 (Year 1), after week 58 through week 102 (Year 2), after week 102 through week 156 (Year 3), after week 156 through week 204 (Year 4), or after week 204 through week 252 (Year 5). c Patients also have LVDr substitutions. d ≥ 1 log10 increase above nadir in HBV DNA by PCR, confirmed with successive measurements or at the end of the windowed time point.
Ir- riżultati jirriflettu l- użu ta ’ doża ta ’ 1 mg ta ’ entecavir għal 147 minn 149 pazjent f’ Sena 3 u fil- pazjenti kollha fi Snin 4 u 5 u ta ’ terapija kkombinata ta ’ entecavir- lamivudine (segwita minn terapija fit- tul b’ entecavir) għal medjan ta ’ 20 ġimgħa għal 130 minn 149 pazjenti f’ Sena 3 u għal ġimgħa waħda għal 1 minn 121 pazjent f’ Sena 4 fi studju rollover. b Jinkludi pazjenti b’ mill- inqas kejl wieħed tad- DNA tal- HBV minn PCT waqt li l- pazjent ikun qed jieħu t- terapija, fi jew wara ġimgħa 24 sa ġimgħa 58 (Sena 1), wara ġimgħa 58 sa ġimgħa 102 (Sena 2), wara ġimgħa 102 sa ġimgħa 156 (Sena 3), wara ġimgħa 156 sa ġimgħa 204 (Sena 4), jew wara ġimgħa 204 sa ġimgħa 252 (Sena 5). c Il- pazjenti għandhom ukoll sostituzzjonijiet LVDr. d żieda ta ’ ≥1 log10 fuq l- inqas ammont fid- DNA tal- HBV minn PCR, ikkonfermat b’ kejl sussegwenti jew fit- tmiem tal - windowed time point.
ETVr substitutions (in addition to LVDr substitutions rtM204V/ I ± rtL180M) were observed at baseline in isolates from 10/ 187 (5%) lamivudine-refractory patients treated with entecavir and monitored for resistance, indicating that prior lamivudine treatment can select these resistance substitutions and that they can exist at a low frequency before entecavir treatment.
Sostituzzjonijiet ETVr (flimkien mas- sostituzzjonijiet LVDr rtM204V/ I ± rtL180M) ġew osservati fil - linja bażika f’ iżolati minn 10/ 187 (5%) pazjenti rifrattorji għal lamivudine ttrattati b’ entecavir u mmonitorjati għar- reżistenza, li juri li t- trattament preċedenti b’ lamivudine jista ’ jagħżel dawn is - sostituzzjonijiet tar- reżistenza u li dawn jistgħu jeżistu bi frekwenza baxxa qabel it- trattament b’ entecavir.
Through Week 240, 3 of the 10 patients experienced virologic breakthrough (≥ 1 log10 increase above nadir).
Sa Ġimgħa 240, 3 mill- 10 pazjenti esperjenzaw breakthrough viroloġiku (żieda ta ’ ≥ 1 log10 ’ il fuq min- nadir).
Emerging entecavir resistance in lamivudine-refractory studies through Week 240 is summarized in the table.
Ir- reżistenza għal entecavir li titfaċċa fl- istudji fuq pazjenti rifrattorji għal lamivudine sa Ġimgħa 240 hija ppreżentata fil- qosor f’ din it- tabella.
11 Genotypic Entecavir Resistance Through Year 5, Lamivudine-Refractory Studies
12 Reżistenza Ġenotipika għal Entecavir Sa Sena 5, Studji dwar Pazjenti Refrattarji għal Lamivudine
Year 3a
Sena 3a
Year 4 a
Sena 4 a
Year 5 a
a
Patients treated and monitored for b resistance Patients in specific year with:
Pazjenti kkurati u mmonitorjati b għal- reżistenza Pazjenti f’ sena speċifika b ’:
c - genotypic ETVr with virologic d breakthrough Cumulative probability of:
c - ETVr ġenotipika bi d breakthrough viroloġiku Probabbiltà kumuluttiva ta ’:
c - genotypic ETVr with virologic d breakthrough a
c - ETVr ġenotipika bi d breakthrough viroloġiku a
1.1%
1. 1%
e 10.7%
e 10. 7%
e 41.3%
e 41. 3%
43.6%
43. 6%
Results reflect use of combination entecavir-lamivudine therapy (followed by long-term entecavir therapy) for a median of 13 weeks for 48 of 80 patients in Year 3, a median of 38 weeks for 10 of 52 patients in Year 4, and for 16 weeks for 1 of 33 patients in Year 5 in a rollover study. b Includes patients with at least one on-therapy HBV DNA measurement by PCR at or after week 24 through week 58 (Year 1), after week 58 through week 102 (Year 2), after week 102 through week 156 (Year 3), after week 156 through week 204 (Year 4), or after week 204 through week 252 (Year 5). c Patients also have LVDr substitutions. d ≥ 1 log10 increase above nadir in HBV DNA by PCR, confirmed with successive measurements or at the end of the windowed time point. e ETVr occurring in any year; virologic breakthrough in specified year.
Ir- riżultati jirriflettu l- użu ta ’ terapija kkombinata b’ entecavir- lamivudine (segwita minn terapija fit- tul b’ entecavir) għal medjan ta ’ 13- il ġimgħa għal 48 minn 80 pazjent f’ Sena 3, medjan ta ’ 38 ġimgħa għal 10 minn 52 pazjent f’ Sena 4, u għal 16- il ġimgħa għal 1 minn 33 pazjent f’ Sena 5 fi studju rollover. b Jinkludi pazjenti b’ mill- inqas kejl wieħed tad- DNA tal- HBV minn PCT waqt li l- pazjent ikun qed jieħu t- terapija, fi jew wara ġimgħa 24 sa ġimgħa 58 (Sena 1), wara ġimgħa 58 sa ġimgħa 102 (Sena 2), wara ġimgħa 102 sa ġimgħa 156 (Sena 3), wara ġimgħa 156 sa ġimgħa 204 (Sena 4), jew wara ġimgħa 204 sa ġimgħa 252 (Sena 5). c Il- pazjenti għandhom ukoll sostituzzjonijiet LVDr. d ≥żieda ta ’ 1 log10 fuq l- inqas ammont fid- DNA tal- HBV minn PCR, ikkonfermat b’ kejl sussegwenti jew fit- tmiem tal - windowed time point. e ETVr li sseħħ fi kwalunkwe sena; breakthrough viroloġiku f’ sena speċifika.
Among lamivudine-refractory patients with baseline HBV DNA < 107 log10 copies/ ml, 64% (9/ 14) achieved HBV DNA < 300 copies/ ml at Week 48.
Fost il- pazjenti refrattarji għal lamivudine b’ DNA tal- HBV fil- linja bażi ta ’ < 107 log10 kopji/ ml, 64% (9/ 14) kisbu DNA tal- HBV ta ’ < 300 kopji/ ml f’ Ġimgħa 48.
Also, lamivudine-refractory patients who achieved HBV DNA < 104 log10 copies/ ml by PCR at Week 24 had a lower rate of resistance than those who did not (5-year cumulative probability 17.6% [n=50] versus 60.5% [n=135], respectively).
Dawn l- 14- il pazjent kellhom rata iktar baxxa ta ’ reżistenza għal entecavir ġenotipiku (probabbiltà kumulattiva ta ’ 18. 8% sa 5 snin ta ’ follow - up) milli fil- popolazzjoni totali tal- istudju (ara t- tabella) Flimkien ma ’ dan, pazjenti refrattarji għal lamivudine li kisbu DNA tal- HBV ta ’ < 104 log10 kopji/ ml minn PCR f’ Ġimgħa 24, kellhom rata ta ’ reżistenza iktar baxxa minn f' dawk li ma kisbuhiex (probabbiltà kumulattiva wara 5 sena ta ’ 17. 6% [n=50] kontra 60. 5% [n=135], rispettivament).
Absorption: entecavir is rapidly absorbed with peak plasma concentrations occurring between 0.5-1.5 hours.
Assorbiment: entecavir jiġi assorbit malajr, bl- ogħla konċentrazzjonijiet fil- plażma jseħħu bejn 0. 5- 1. 5 sigħat.
The absolute bioavailability has not been determined.
Il- bijodisponibiltà assoluta ma ġietx stabbilita.
Based on urinary excretion of unchanged drug, the bioavailability has been estimated to be at least 70%.
Fuq il- bażi ta ’ l- eskrezzjoni urinarja ta ’ droga mhux mibdula, il- bijodisponibilità ġiet stmata li minn ta ’ l- inqas hi 70%.
There is a dose- proportionate increase in Cmax and AUC values following multiple doses ranging from 0.1-1 mg.
Hemm żjieda proporzjonata mad- doża f’ Cmas u l- valuri ta ’ l- AUC wara numru ta ’ dożi li jvarjaw minn 0. 1- 1 mg.
Steady-state is achieved between 6-10 days after once daily dosing with ≈ 2 times accumulation.
Konċentrazzjoni fissa tintlaħaq bejn 6- 10t’ ijiem wara doża waħda kuljum għal bejn wieħed u ieħor id - doppju.
Cmax and Cmin at steady-state are 4.2 and 0.3 ng/ ml, respectively, for a dose of 0.5 mg, and 8.2 and 0.5 ng/ ml, respectively, for 1 mg.
Cmas u Cmin f’ konċentrazzjoni fissa huma 4. 2 u 0. 3 ng/ ml, rispettivament, għal doża ta ’ 0. 5mg, u 8. 2 u 0. 5ng/ ml, rispettivament għal 1mg.
The tablet and oral solution were bioequivalent in healthy subjects; therefore, both forms may be used interchangeably.
Il- pillola u s- soluzjoni orali huma bijoekwivalenti f’ suġġetti b’ saħħithom; għalhekk iż- żewġ forom jistgħu jissostitwixxu lil xulxin.
0.75 hour fasted), a decrease in Cmax of 44-46%, and a decrease in AUC of 18-20%.
Għoti ta ’ 0. 5 mg ta ’ entecavir ma ’ ikla standard b’ ħafna xaħam (945 kcal, 54. 6 g ta ’ xaħam) jew ikla ħafifa (379 kcal, 8. 2 g xaħam) irriżulta f’ dewmien minimu fl- assorbiment (1- 1. 5 sigħat bl- ikel vs 0. 75 sigħat sajma), u tnaqqis f’ Cmas ta ’ 44- 46%, u tnaqqis f’ AUC ta ’ 18- 20%.
The lower Cmax and AUC when taken with food is not considered to be of clinical relevance in nucleoside-naive patients but could affect efficacy in lamivudine-refractory patients (see section 4.2).
Is- Cmas il- baxx u l- AUC meta jittieħdu ma ’ l- ikel mhumiex ikkunsidrati ta ’ relevanza klinika f’ pazjenti li huma nucleoside naïve imma jistgħu jaffetwaw l- effikaċja f’ pazjenti reffrattorji għal lamivudine (ara sezzjoni 4. 2).
Distribution: the estimated volume of distribution for entecavir is in excess of total body water.
Distribuzzjoni: il- volum stmat tad- distribuzzjoni ta ’ entecavir huwa iżjed mill- volum totali ta ’ ilma fil - ġisem.
Protein binding to human serum protein in vitro is ≈ 13%.
Ir- rabta ta ’ entecavir mal- proteini fis- serum uman in vitro huwa ta ’ madwar 13%.
Metabolism: entecavir is not a substrate, inhibitor or inducer of the CYP450 enzyme system.
13 Metaboliżmu: entecavir mhuwiex sottostrat, inibitur jew inducer tas- sistema ta ’ enżimi CYP450.
Following administration of 14C-entecavir, no oxidative or acetylated metabolites and minor amounts of the phase II metabolites, glucuronide and sulfate conjugates, were observed.
Wara l- għoti ta ’ 14C- entecavir, l- ebda metaboliti ta ’ ossidazzjoni jew ta ’ aċitilizzazzjoni u ammonti żgħar ta ’ metaboliti tat- tieni fażi ma ġew osservati.
12 Elimination: entecavir is predominantly eliminated by the kidney with urinary recovery of unchanged drug at steady-state of about 75% of the dose.
Eliminazzjoni: entecavir huwa eliminat b’ mod predominanti mill- kliewi b’ irkupru tad- droga mhux mibdula mill- awrina f’ konċentrazzjoni fissa ta ’ madwar 75% tad- doża.
Renal clearance is independent of dose and ranges between 360-471 ml/ min suggesting that entecavir undergoes both glomerular filtration and net tubular secretion.
Il- clearance tal- kliewi huwa indipendenti mid- doża u jvarja bejn 360- 471 ml/ min; dan jissuġġerixxi li entecavir jintrema fl- urina kemm minn filtrazzjoni glomerulari kif ukoll minn sekrezzjoni netta tubulari.
After reaching peak levels, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of ≈ 128-149 hours.
Wara li jilħqu l- ogħla livelli, il- konċentrazzjonijiet ta ’ entecavir fil- plażma jitbaxxew b’ mod bi- esponenzjali b’ half- life ta ’ l - eliminazzjoni terminali ta ’ ≈ 128- 149 sigħat.
The observed drug accumulation index is ≈ 2 times with once daily dosing, suggesting an effective accumulation half-life of about 24 hours.
L- indiċi ta ’ l- akkumulazzjoni tad- droga osservat kien ≈ darbtejn dak ta ’ b’ doża waħda kuljum; dan jissuġġerixxi half- life ta ’ akkumulazzjoni effettiva ta ’ bejn wieħed u ieħor, 24 siegħa.
Hepatic impairment: pharmacokinetic parameters in patients with moderate or severe hepatic impairment were similar to those in patients with normal hepatic function.
Indeboliment tal- fwied: il- parametri farmakokinetiċi f’ pazjenti b’ indeboliment moderat jew gravi tal - fwied kienu simili għal ta ’ dawk f’ pazjenti b’ funzjoni normali.
Renal impairment: entecavir clearance decreases with decreasing creatinine clearance.
Indeboliment tal- kliewi: il- clearance ta ’ entecavir skond il- clearance tal- kreatinina.
A 4 hour period of haemodialysis removed ≈ 13% of the dose, and 0.3% was removed by CAPD.
Perijodu ta ’ 4 sigħat ta ’ emodijaliżi neħħa ≈ 13% tad- doża, u 0. 3% tneħħew b’ CAPD.
The pharmacokinetics of entecavir following a single 1 mg dose in patients (without chronic hepatitis B infection) are shown in the table below:
Il- farmakokinetika ta ’ entecavir wara doża waħda ta ’ 1 mg f’ pazjenti mingħajr infezzjoni kronika ta ’ l- epatite B jidhru fit - tabella:
Baseline Creatinine Clearance (ml/ min)
Clearance tal- Kreatinina ta ’ Linja Bażi (ml/ min) Moderat
Moderate
Ħafif
Severe Severe
Sever Sever
≤ 80
30- 50
Haemodialysis
Immaniġġjat b’ Emodijaliżi
with CAPD
Immaniġġj at b’ CAPD
Cmax (ng/ ml) (CV%)
Cmas (ng/ ml) (CV%)
8.1 (30.7)
8. 1 (30. 7)
10.5 (22.7)
10. 4 (37. 2)
15.3 (33.8)
10. 5 (22. 7)
15.4 (56.4)
15. 3 15. 4 (33. 8) (56. 4)
16.6 (29.7)
16. 6 (29. 7)
27.9
27. 9
51.5
51. 5
69.5
69. 5
233.9
145. 7 233. 9
221.8
221. 8
(22.8)
(25. 6)
(22.7)
(22. 8)
(31.5)
(22. 7)
(28.4)
(31. 5) (28. 4)
(11.6)
(11. 6)
383.2
383. 2 (101. 8)
197.9
197. 9 (78. 1)
135.6
135. 6 (31. 6)
NA
40. 3 NA (10. 1)
588.1
588. 1
309.2
309. 2
226.3
226. 3
100.6
100. 6
50.6
50. 6
35.7
35. 7
(153.7)
(153. 7)
(62.6)
(62. 6)
(60.1)
(60. 1)
(29.1)
(29. 1)
(16.5)
(16. 5)
(19.6)
(19. 6)
Post-Liver transplant: entecavir exposure in HBV-infected liver transplant recipients on a stable dose of cyclosporine A or tacrolimus (n = 9) was ≈ 2 times the exposure in healthy subjects with normal renal function.
9 pazjenti li kellhom bżonn trapjant tal- fwied minħabba HBV u kienu fuq doża stabbli ta ’ cyclosporine A jew tacrolimus, kellhom bżonn ta ’ doża ta ’ entecavir id- doppju jekk kellhom mard tal fwied milli kieku ma kellhomx.
Altered renal function contributed to the increase in entecavir exposure in these patients (see section 4.4).
(ara sezzjoni 4. 4).
AUC was 14% higher in women than in men, due to differences in renal function and weight.
L- AUC kien 14% ogħla fin- nisa meta mqabbel ma ’ dak ta ’ l- irġiel, minħabba d- differenzi fil - funzjoni renali u fil- piż.
After adjusting for differences in creatinine clearance and body weight there was no difference in exposure between male and female subjects.
Wara aġġustament għad- differenzi fil- clearance tal- kreatinina u l- piż tal - ġisem ma kien hemm ebda differenza fid- doża bejn nisa u rġiel.
Elderly: the effect of age on the pharmacokinetics of entecavir was evaluated comparing elderly subjects in the age range 65-83 years (mean age females 69 years, males 74 years) with young subjects in the age range 20-40 years (mean age females 29 years, males 25 years).
Anzjani: l- effett ta ’ l- età fuq il- farmakokinetika ta ’ entecavir ġie evalwat billi suġġetti anzjani ta’ età bejn 65- 83 (età medja ta ’ 69 fin- nisa, 74 fl- irġiel) tqabblu ma ’ suġġetti li għadhom żgħar fl- età, jiġifieri ta ’ bejn 20- 40 sena (età medja ta ’ 29 fin- nisa, 25 fl- irġiel).
AUC was 29% higher in elderly than in young subjects, mainly due to differences in renal function and weight.
L- AUC kien 29% ogħla fl- anzjani milli fis- suġġetti li għadhom żgħar, l- iktar minħabba d- differenzi fil- funzjoni renali u l- piż.
After adjusting for differences in creatinine clearance and body weight, elderly subjects had a 12.5% higher AUC than young subjects. The population pharmacokinetic analysis covering patients in the age range 16-75 years did not identify age as significantly influencing entecavir pharmacokinetics.
L- analiżi farmakokinetika tal- popolazzjoni li kopriet pazjenti ta ’ età bejn 16- 75 sena ma wrietx li l- età għandha effett b’ mod sinifikanti fuq il- farmakokinetika ta ’ entecavir.
Race: the population pharmacokinetic analysis did not identify race as significantly influencing entecavir pharmacokinetics.
14 Razza: l- analiżi farmakokinetika tal- popolazzjoni ma wrietx li r- razza għandha effett b’ mod sinifikanti fuq il- farmakokinetika ta ’ entecavir.
However, conclusions can only be drawn for the Caucasian and Asian groups as there were too few subjects in the other categories.
Madankollu l- konklużjonijiet jistgħu jsiru biss għall- gruppi Asjatiċi u Kawkażi għax kien hemm ftit wisq suġġetti fil- kategoriji l- oħra.
In repeat-dose toxicology studies in dogs, reversible perivascular inflammation was observed in the central nervous system, for which no-effect doses corresponded to exposures 19 and 10 times those in humans (at 0.5 and 1 mg respectively).
Fi studji tossikoliġiċi b’ dożi ripetuti fuq il- klieb, ġiet osservata infjammazzjoni perivaskulari riversibbli fis- sistema nervuża ċentrali, li għaliha, dożi bla effett ikkorrispondew għal dożi ta ’ 19 u 10 darbiet dawk fl- umani (f’ 0. 5 u 1 mg rispettivament).
This finding was not observed in repeat-dose studies in other species, including monkeys administered entecavir daily for 1 year at exposures ≥ 100 times those in humans.
Dan l- effett ma deherx fi studji b’ dożi ripetuti fi speċi oħra, inklużi xadini li ngħataw entecavir kuljum għal sena b’ dożi ≥ 100 darba dawk fl- umani.
In reproductive toxicology studies in which animals were administered entecavir for up to 4 weeks, no evidence of impaired fertility was seen in male or female rats at high exposures.
Fi studji riproduttivi tossikoloġiċi, li fihom l- annimali ngħataw entecavir għal mhux iktar minn 4 ġimgħat, ma kien hemm ebda sinjali ta ’ nuqqas ta ’ fertilità fil- firien irġiel jew nisa wara dożi għoljin.
Testicular changes (seminiferous tubular degeneration) were evident in repeat-dose toxicology studies in rodents and dogs at exposures ≥ 26 times those in humans.
Bidliet testikolari (deġenerazzjoni tubulari seminiferuża) kienu evidenti fi studji tossikoloġiċi b’ doża ripetuta f’ annimali li jgerrmu u klieb b’ dozi ≥ 26 darba dawk fl- umani.
No testicular changes were evident in a 1-year study in monkeys.
Ebda tibdil testikolari ma kien evidenti fi studju ta ’ sena fix- xadini.
In pregnant rats and rabbits administered entecavir, no effect levels for embryotoxicity and maternal toxicity corresponded to exposures ≥ 21 times those in humans.
F’ firien u fniek tqal li ngħataw entecavir, il- livelli ta ’ bla effett għall- embrijotossiċità u għat- tossiċità materna jikkorrispondu għal dożi ≥ 21 darba dawk fl- umani.
In rats, maternal toxicity, embryo- foetal toxicity (resorptions), lower foetal body weights, tail and vertebral malformations, reduced ossification (vertebrae, sternebrae, and phalanges), and extra lumbar vertebrae and ribs were observed at high exposures.
Fil- firien, ġew osservati tossiċità materna, tossiċità embrijo- fetali (riassorbimenti), piż inqas tal- ġisem tal- fetu, malformazzjonijiet fid - denb u vertebri, ossifikazzjoni imnaqqsa (vertebri, sternebrae u flanġi) u vertebra tal- ġenbejn u kustilji addizzjonali wara dożi qawwija.
In rabbits, embryo-foetal toxicity (resorptions), reduced ossification (hyoid), and an increased incidence of 13th rib were observed at high exposures.
Fil- fniek, tossiċità embrijo- fetali (assorbiment mill- ġdid), ossifikazzjoni imnaqqsa (hyoid), u inċidenza ikbar tat- 13- il kustilja ġew osservati b’ dożi qawwija.
In a peri-postnatal study in rats, no adverse effects on offspring were observed.
Fi studji fuq il- firien eżattament wara t- twelid tagħhom, ma ġew osservati ebda effetti ta ’ dannu fil- frieħ.
In a separate study wherein entecavir was administered to pregnant lactating rats at 10 mg/ kg, both foetal exposure to entecavir and secretion of entecavir into milk were demonstrated.
Fi studju separat fejn entecavir ingħata b’ doża ta ’ 10mg/ kg lil firien tqal u li kienu qed ireddgħu, entecavir instab kemm fil- fetu kif ukoll fil- ħalib tal- omm.
No evidence of genotoxicity was observed in an Ames microbial mutagenicity assay, a mammalian- cell gene mutation assay, and a transformation assay with Syrian hamster embryo cells.
L- ebda evidenza ta ’ ġenotossiċità ma ġiet osservata f’ Ames microbial mutagenicity assay, cell gene mutation cell assay tal- mammiferi u transformation assay b’ ċelloli embrijoniċi ta ’ ħamsters tas- Sirja.
A micronucleus study and a DNA repair study in rats were also negative.
Studju tal- mikronukleju u studju tat- tiswija tad- DNA fil- firien kienu negattivi ukoll.
Entecavir was clastogenic to human lymphocyte cultures at concentrations substantially higher than those achieved clinically.
Entecavir kien klastoġeniku għal kulturi tal- limfoċiti umani f’ konċentrazzjonijiet sostanzjalment ogħla minn dawk li ntlaħqu klinikalment.
Two-year carcinogenicity studies: in male mice, increases in the incidences of lung tumours were observed at exposures ≥ 4 and ≥ 2 times that in humans at 0.5 mg and 1 mg respectively.
Studji ta’ sentejn fuq il- karċinoġeniċità: fi ġrieden irġiel, ġew osservati żjidiet fl- inċidenza ta ’ tumuri tal- pulmun b’ dożi ta ’ ≥ 4 u ≥ darbtejn dawk fl- umani b’ doża ta ’ 0. 5 mg u 1 mg rispettivament.
Tumour development was preceded by pneumocyte proliferation in the lung which was not observed in rats, dogs, or monkeys, indicating that a key event in lung tumour development observed in mice likely was species-specific.
Qabel l- iżvilupp ta ’ tumuri kien hemm proliferazzjoni tal- pneumoċiti fil- pulmun li ma ġietx osservata fil - firien, fil- klieb jew fix- xadini, u dan jindika li dan l- avveniment prinċipali fl- iżvilupp ta ’ tumur fil - pulmun osservat fil- ġrieden probabbli huwa speċifiku għall- ispeċi.
Increased incidences of other tumours including brain gliomas in male and female rats, liver carcinomas in male mice, benign vascular tumours in female mice, and liver adenomas and carcinomas in female rats were seen only at high lifetime exposures.
Inċidenzi ogħla ta ’ tumuri oħra inklużi glijomi tal- moħħ f’ firien nisa u rġiel, karċinomi tal- fwied fi ġrieden irġiel, tumuri vaskulari beninji fi ġrieden nisa u adenoma u karċinomi tal- fwied f’ firien nisa, dehru biss b’ dożi qawwija matul ħajjithom.
However, the no effect levels could not be precisely established.
Madankollu l- livelli ta ’ bla effett ma setgħux jiġu stabbiliti b’ mod preċiż.
The predictivity of the findings for humans is not known.
Il- possibbiltà li jsir tbassir minn dawn is- sejbiet fuq l- umani għadha mhiex magħrufa.
Crospovidone Lactose monohydrate Magnesium stearate Cellulose, Microcrystalline Povidone
Crospovidone Lactose monohydrate Magnesium stearate Cellulose, Microcrystalline Povidone
Titanium dioxide Hypromellose Macrogol 400 Polysorbate 80 (E433)
15 Titanium dioxide Hypromellose Macrogol 400 Polysorbate 80 (E433)
Store in the original carton.
Aħżen fil- pakkett oriġinali.
Bottles:
Kontenituri:
Each carton contains either:
Kull kartuna fiha jew:
30 x 1 film-coated tablets; 3 blister cards of 10 x 1 film-coated tablets each in Alu/ Alu perforated unit dose blisters, or 90 x 1 film-coated tablets; 9 blister cards of 10 x 1 film-coated tablets each in Alu/ Alu perforated unit dose blisters.
30 x 1 pillola miksija b’ rita; 3 folji ta ’ 10 x 1 pillola miksija b’ rita, kull waħda f’ folji ta ’ doża waħda, mtaqqbin ta ’ Alu/ Alu, jew 90 x 1 pillola miksija b’ rita; 9 folji ta ’ 10 x 1 pillola miksija b’ rita, kull waħda f’ folji ta ’ doża waħda, mtaqqbin ta ’ Alu/ Alu.
High-density polyethylene (HDPE) bottle with child resistant polypropylene closure containing 30 film-coated tablets.
Flixkun ta ’ high- density polyethylene (HDPE) b’ għeluq tal- polypropylene magħmul apposta biex it - tfal ma jkunux jistgħu jiftħuħ, li fih 30 pillola miksija b’ rita.
Not all pack sizes and container types may be marketed.
Jista jkun li mhux il- pakketti tad- daqsijiet kollha u t- tipi ta ’ kontenituri kollha jkunu għall- skop kummerċjali.
Blister packs:
Pakkett tal- folji:
EU/ 1/ 06/ 343/ 003 EU/ 1/ 06/ 343/ 006
EU/ 1/ 06/ 343/ 003 EU/ 1/ 06/ 343/ 006 Pakkett tal- flixkun: EU/ 1/ 06/ 343/ 001
26 June 2006
26 ta ’ Ġunju 2006
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
Informazzjoni ddettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
Baraclude 1 mg film-coated tablets
Baraclude 1 mg pilloli miksijin b’ rita
Each tablet contains 1 mg entecavir (as monohydrate).
Kull pillola fiha 1 mg entecavir (bħala monoidrat).
Excipients: each tablet contains 241 mg lactose.
Sustanzi mhux attivi: kull pillola fiha 241 mg ta ’ lactose.
Pink and triangular-shaped tablet with “ BMS ” debossed on one side and “ 1612” on the other.
Pillola ta ’ lewn Roża f’ għamla triangolari b ’ “ BMS ” imnaqqxa fuq naħa u “ 1612 ” fuq in- naħa l- oħra.
With prolonged treatment for more than 2 years, regular reassessment is recommended to confirm that continuing the selected therapy remains appropriate for the patient.
Bi trattment imtawwal għal iktar min sentejn, hija rrakkomandata valutazzjoni mill- ġdid biex jiġi kkonfermat li t- tkomplija tat- terapija magħżula tibqa ’ tajba għall- pazjent.
After initiating antiviral therapy, serum ALT may increase in some patients as serum HBV DNA levels decline (see section 4.8).
Wara li tinbeda t- terapija antivirali, l- ALT fis - serum f’ xi pazjenti jista ’ jiżdied, filwaqt li l- livelli ta ’ DNA ta ’ HBV fis- serum jonqsu (ara sezzjoni 4. 8).
In patients with compensated liver disease, these increases in serum ALT are generally not accompanied by an increase in serum bilirubin concentrations or hepatic decompensation.
F’ pazjenti b’ mard tal- fwied ikkumpensat, dawn iż- żidiet fl- ALT fis- serum
18 Acute exacerbation of hepatitis has also been reported in patients who have discontinued hepatitis B therapy.
Taħrix akut ta ’ l- epatite ġie rrappurtat ukoll f’ pazjenti li waqqfu t- terapija għal epatite B.
Liver transplant recipients: there are limited data on efficacy and safety of entecavir in liver transplant recipients.
20 Riċevituri ta ’ trapjant tal- fwied: hemm ftit tagħrif fuq l- effikaċja u s- sigurtà ta ’ entecavir f’ riċevituri ta ’ trapjant tal- fwied.
Lactose: this medicinal product contains 241 mg of lactose in each 1 mg daily dose.
Lactose: dan il- prodott mediċinali fih 241 mg ta ’ lactose f’ kull doża ta ’ kuljum ta ’ 1 mg.
Given that the potential risks to the developing foetus are unknown, women of child-bearing potential should use effective contraception.
21 Minħabba li r- riskji potenzjali fuq il- fetu li jkun qed jiżviluppa m’ humiex magħrufa, nisa li għandhom il- potenzjal li jkollhom it- tfal iridu jużaw kontraċezzjoni effettiva.
20 4.8 Undesirable effects
4. 8 Effetti mhux mixtieqa
Experience in lamivudine-refractory patients:
22 Esperjenza f’ pazjenti li huma refrattarji għal lamivudine:
21 Treatment beyond 48 weeks: continued treatment with entecavir for a median duration of 96 weeks did not reveal any new safety signals.
Trattament itwal minn 48 ġimgħa: kontinwazzjoni ta ’ trattament b’ entecavir għal tul medju ta ’ 96 ġimgħa ma wrietx sinjali ġodda dwar is- sigurtà tiegħu.
Decompensated cirrhosis: a higher rate of serious hepatic adverse events has been observed in patients with decompensated cirrhosis compared with rates in patients with compensated liver function.
23 Ċirrożi di- kumpensata: rata ogħla ta ’ avvenimenti avversi epatiċi serji ġiet osservata f’ pazjenti b’ ċirrożi di- kumpensata meta mqabbla ma ’ rati f’ pazjenti b’ funzjoni tal- fwied ikkumpensata.
Resistance in cell culture: relative to wild-type HBV, LVDr viruses containing rtM204V and rtL180M substitutions within the reverse transcriptase exhibit 8-fold decreased susceptibility to entecavir.
24 Reżistenza f’ kultura ta ’ ċelloli: fir- rigward ta ’ HBV wild- type, virusijiet LVDr li fihom sostituzzjonijiet ta ’ rtM204V u rtL180M fir- reverse transcriptase juru suxxettibilità ta ’ 8 darbiet inqas għal entecavir.
Experience in lamivudine-refractory patients:
25 Esperjenza f’ pazjenti li huma refrattarji għal lamivudine:
Patients in response were followed for an additional 24 weeks off-
Il- kriterji kienu tnaqqis tal- virus HBV (DNA ta ’ HBV < 0. 7 MEq/ ml minn bDNA) u tnaqqis fl- HBeAg (f’ pazjenti pożittivi għall- HBeAg) jew ALT < 1. 25 drabi l- ULN (f’ pazjenti negattivi għall- HBeAg).
24 treatment.
Pazjenti b’ rispons pożittiv ġew segwiti għal 24 ġimgħa oħra bla trattament.
For patients who met protocol-defined response criteria, response was sustained throughout the 24-week post-treatment follow-up in 75% (83/ 111) of entecavir responders vs 73% (68/ 93) for lamivudine responders in study 022 and 46% (131/ 286) of entecavir responders vs 31% (79/ 253) for lamivudine responders in study 027.
26 Għal pazjenti li ssodisfaw il- kriterji li ġew definiti fi protokoll, it- titjib kompla matul il- follow- up ta ’ 24 ġimgħa wara t- trattament f’ 75% (83/ 111) tal- pazjenti li rrispondew għal entecavir kontra 73% (68/ 93) għal dawk li rrispondew għal lamivudine fi studju 022 u 46% (131/ 286) ta ’ dawk li rrispondew għal entecavir meta mqabbel ma ’ 31% (79/ 253) għal pazjenti li rrispondew għal lamivudine fi studju 027.
25 HIV/ HBV co-infected patients not receiving concomitant HAART: entecavir has not been evaluated in HIV/ HBV co-infected patients not concurrently receiving effective HIV treatment.
Pazjenti ko- infettati bl- HIV/ HBV li ma jkunux qed jingħataw HAART fl- istess ħin: entecavir ma ġiex evalwat f’ pazjenti infettati fl- istess ħin bl- HIV/ HBV li ma kinux qegħdin jirċievu fl- istess ħin kura effettiva kontra l- HIV.
Emerging Genotypic Entecavir Resistance Through Year 5, Nucleoside-Naive Studies a
27 Reżistenza Ġenotipika Ġdida għal Entecavir Sa Sena 5, Studji dwar Pazjenti li Qatt ma Ħadu Nukleoside a
26 Genotypic Entecavir Resistance Through Year 5, Lamivudine-Refractory Studies
28 Reżistenza Ġenotipika għal Entecavir Sa Sena 5, Studji dwar Pazjenti Refrattarji għal Lamivudine
Metabolism: entecavir is not a substrate, inhibitor or inducer of the CYP450 enzyme system.
29 Metaboliżmu: entecavir mhuwiex sottostrat, inibitur jew inducer tas- sistema ta ’ enżimi CYP450.
27 Elimination: entecavir is predominantly eliminated by the kidney with urinary recovery of unchanged drug at steady-state of about 75% of the dose.
Eliminazzjoni: entecavir huwa eliminat b’ mod predominanti mill- kliewi b’ irkupru tad- droga mhux mibdula mill- awrina f’ konċentrazzjoni fissa ta ’ madwar 75% tad- doża.
Race: the population pharmacokinetic analysis did not identify race as significantly influencing entecavir pharmacokinetics.
30 Razza: l- analiżi farmakokinetika tal- popolazzjoni ma wrietx li r- razza għandha effett b’ mod sinifikanti fuq il- farmakokinetika ta ’ entecavir.
28 5.3 Preclinical safety data
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
Titanium dioxide Hypromellose Macrogol 400 Iron oxide red
31 Titanium dioxide Hypromellose Macrogol 400 Iron oxide red
EU/ 1/ 06/ 343/ 004 EU/ 1/ 06/ 343/ 007
EU/ 1/ 06/ 343/ 004 EU/ 1/ 06/ 343/ 007 Pakkett tal- flixkun: EU/ 1/ 06/ 343/ 002
Baraclude 0.05 mg/ ml oral solution
Baraclude 0. 05 mg/ ml soluzzjoni orali
Each ml oral solution contains 0.05 mg entecavir (as monohydrate).
Kull ml tas- soluzzjoni orali fih 0. 05 mg entecavir (bħala monoidrat).
650 mg maltitol liquid/ ml 2 mg methylhydroxybenzoate/ ml 0.28 mg propylhydroxybenzoate/ ml
650 mg maltitol liquid/ ml 2 mg methylhydroxybenzoate/ ml 0. 28 mg propylhydroxybenzoate/ ml
of excipients, see section 6.1.
Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Clear, colourless to pale yellow solution
Soluzzjoni ċara, bla kulur għal isfar ċar
This indication is based on clinical trial data in nucleoside naive patients with HBeAg positive and HBeAg negative HBV infection.
Din l- indikazzjoni hija bbażata fuq tagħrif minn provi kliniċi fuq pazjenti nucleoside naïve li għandhom infezzjoni bl- HBV, kemm pożittivi għal HBeAg kif ukoll negattivi għal HbeAg.
It is recommended that the dosing spoon be rinsed with water after each daily dose.
Huwa rrakkomandat li l- imgħarfa għall- qies tiġi mlaħalħa bl- ilma wara kull doża li tieħu.
With prolonged treatment for more than 2 years, regular
34 F’ pazjenti li jirriżultaw negattivi għal HBeAg, it- trattament irid jingħata għallinqas sakemm ikun hemm serokonverżjoni ta ’ HBs jew sakemm ikun hemm evidenza ta ’ nuqqas fl- effikaċja.
32 reassessment is recommended to confirm that continuing the selected therapy remains appropriate for the patient.
Bi trattment imtawwal għal iktar min sentejn, hija rrakkomandata valutazzjoni mill- ġdid biex jiġi kkonfermat li t- tkomplija tat- terapija magħżula tibqa ’ tajba għall- pazjent.
Baraclude is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.
Baraclude mhux irrakkomandat għall- użu fit- tfal u adoloxxenti taħt it- tmintax- il sena peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja.
Baraclude dosage
Doża ta ’ Baraclude
0.5 mg once daily 0.25 mg once daily OR
darba kuljum JEW
0.5 mg every 48 hours
0. 5 mg kull 48 siegħa
0.15 mg once daily OR
0. 15 mg
0.3 mg
darba kuljum JEW
once daily OR
0. 3 mg darba kuljum JEW
0.5 mg every 72 hours
0. 5 mg kull 72 siegħa
0.05 mg once daily
0. 05 mg darba kuljum
0.1 mg once daily
0. 1mg darba kuljum
Haemodialysis or
Emodijaliżi jew
0.5 mg every 5-7 days
0. 5 mg kull 5 – 7t ijiem
**on haemodialysis days, administer entecavir after haemodialysis.
** fi ġranet ta ’ emodijaliżi, agħti entecavir wara emodijaliżi.
After initiating antiviral therapy, serum ALT may increase in some patients as serum HBV DNA levels decline (see section 4.8).
35 serum f’ xi pazjenti jista ’ jiżdied, filwaqt li l- livelli ta ’ DNA ta ’ HBV fis- serum jonqsu (ara sezzjoni 4. 8).
Patients with cirrhosis
F’ pazjenti b’ mard tal- fwied ikkumpensat, dawn iż- żidiet fl- ALT fis- serum ġeneralment m’ humiex akkumpanjati b’ żjieda fil- konċentrazzjonijiet tal- bilirubin fis- serum jew b’ di - kumpensazzjoni epatika.
33 may be at a higher risk for hepatic decompensation following hepatitis exacerbation, and therefore should be monitored closely during therapy.
Pazjenti b’ ċirrożi jistgħu jkunu f’ riskju ikbar għal di- kumpensazzjoni epatika wara taħrix ta ’ l- epatite, u għalhekk jeħtieġu jiġu immonitorjati b’ attenzjoni waqt it- terapija.
Acute exacerbation of hepatitis has also been reported in patients who have discontinued hepatitis B therapy.
Taħrix akut ta ’ l- epatite ġie rrappurtat ukoll f’ pazjenti li waqqfu t- terapija għal epatite B.
Patients with decompensated cirrhosis: a higher rate of serious hepatic adverse events has been observed in patients with decompensated cirrhosis compared with rates in patients with compensated liver function.
Pazjenti b’ ċirrożi di- kumpensata: rata ogħla ta ’ avvenimenti avversi epatiċi serji ġiet osservata f’ pazjenti b’ ċirrożi di- kumpensata meta mqabbla ma ’ rati f’ pazjenti b’ funzjoni tal- fwied ikkumpensata.
This observation is based on limited experience in 45 patients with Child-Pugh score ≥ 7 at the start of entecavir treatment.
Din l- osservazjoni hija bbażata fuq esperjenza limitata f’ 45 pazjent b’ Child Pugh score ≥ 7 fil- bidu tat- trattament b’ entecavir.
These patients should be regularly monitored for clinical, virological and serological parameters associated with hepatitis B, liver and renal function and antiviral response during treatment, and if treatment is discontinued, for at least 6 months thereafter.
Dawn il- pazjenti għandhom jiġu mmonitorjati regolarment għal parametri kliniċi, viroloġiċi u tas- serum assoċjati ma ’ l- epatite B, il- funzjoni tal- fwied u tal- kliewi u l - effett antivirali waqt it- trattament, u jekk it- trattament jitwaqqaf, dawn il- pazjenti għandhom jiġu immonitorjati regolarment għal sitt xhur wara li dan iseħħ.
Lactic acidosis and severe hepatomegaly with steatosis: occurrences of lactic acidosis (in the absence of hypoxaemia), sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues.
Aċidożi lattika u epatomegalija severa b’ steatożi: bi steatożi: okkorrenzi ta ’ aċidożi lattika (mingħajr hypoxaemia), xi kultant fatali, li s- soltu huma assoċjati ma ’ epatomegalija gravi u ma ’ stenożi epatika, ġew irrapportati bl- użu ta ’ nucleoside analogues.
Resistance and specific precaution for lamivudine-refractory patients: mutations in the HBV polymerase that encode lamivudine-resistance substitutions may lead to the subsequent emergence of secondary substitutions, including those associated with entecavir associated resistance (ETVr).).
Reżistenza u prekawzjonijiet speċifiċi għall- pazjenti li huma rifrattarji għal lamivudine: mutazzjonijiet fl- HBV polymerase li jirriżultaw f’ sostituzzjonijiet li jsarrfu f’ reżistenza għal lamivudine jistgħu iwasslu għall- feġġa sussegwenti ta ’ sostituzzjonijiet sekondarji, inklużi dawk assoċjati ma ’ reżistenza assoċjata ma ’ entecavir (ETVr).
Patients with lamivudine-resistant HBV are at higher risk of developing subsequent entecavir resistance than patients without lamivudine-resistance.
Pazjenti b’ HBV reżistenti għal lamivudine, huma f’ riskju ogħla li jiżviluppaw reżistenza sussegwenti għal kura b’ entecavir milli pazjenti mingħajr reżistenza għal lamivudine.
In patients with a suboptimal virological response after 24 weeks of treatment with entecavir, a modification of treatment should be considered (see sections 4.5 and 5.1).
36 wieħed wara 24 ġimgħa ta ’ kura b’ entecavir, għandu jiġi kkunsidrat tibdil tal- kura (ara sezzjonijiet 4. 5 u 5. 1).
Liver transplant recipients: there are limited data on efficacy and safety of entecavir in liver transplant recipients.
Riċevituri ta ’ trapjant tal- fwied: hemm ftit tagħrif fuq l- effikaċja u s- sigurtà ta ’ entecavir f’ riċevituri ta ’ trapjant tal- fwied.
34 Human immunodeficiency virus (HIV)/ HBV co-infected patients not receiving concomitant antiretroviral therapy: entecavir has not been evaluated in HIV/ HBV co-infected patients not concurrently receiving effective HIV treatment.
Pazjenti infettati bil- virus ta ’ l- immunodefiċjenza umana (HIV) / HBV li ma jkunux jingħataw kura antiretrovirali fl- istess ħin: entecavir ma ġiex evalwat f’ pazjenti infettati bl- HIV/ HBV li ma kinux qegħdin jieħdu kura effettiva fl- istess ħin kontra l- HIV.
There are limited data on patients co-infected with HIV who have low CD4 cell counts (< 200 cells/ mm3).
Hemm ftit tagħrif fuq pazjenti li huma infettati wkoll bl- HIV li għandhom ammont baxx ta ’ ċelloli CD4 (< 200 ċelloli/ mm3.
Baraclude oral solution contains maltitol (13 g maltitol liquid per 20 ml dose).
Baraclude soluzzjoni orali fiha maltitol (13 g ta ’ maltitol likwidu għal kull doża ta ’ 20 ml).
Baraclude may have a mild laxative effect.
Baraclude jista ’ jkollu effett lassattiv ħafif.
Calorific value 2.3 kcal/ g maltitol.
Valur kalorifiku 2. 3 kcal/ g maltitol.
Baraclude tablets do not contain maltitol and can be taken by patients with fructose intolerance.
Il- pilloli Baraclude ma fihomx maltitol u jistgħu jittieħdu minn pazjenti li ma jistgħux jieħdu fructose.