qanastek/EMEA-V3 huggingface dataset:
* for doses < 0.5 mg Baraclude oral solution is recommended. ** on haemodialysis days, administer entecavir after haemodialysis.
* għal dożi inqas min 0. 5 mg ta ’ Baraclude, soluzzjoni orali hija rrakkomandata. ** fi ġranet ta ’ emodijaliżi, agħti entecavir wara emodijaliżi.
Hepatic impairment: no dose adjustment is required in patients with hepatic impairment.
Indeboliment tal- fwied: l- ebda aġġustament fid- doża m’ huwa meħtieġ f’ pazjenti b’ indeboliment tal - fwied.
Renal impairment: dosage adjustment is recommended for patients with renal impairment (see section 4.2).
Indeboliment tal- kliewi: huwa rrakkomandat aġġustament fid- doża għal pazjenti b’ indeboliment renali (ara sezzjoni 4. 2).
The proposed dose modifications are based on extrapolation of limited data, and their safety and effectiveness have not been clinically evaluated.
Il- modifikazzjonijiet proposti fid- doża huma bbażati fuq estrapolazzjoni ta ’ informazzjoni limitata, u s- sigurtà u l- effikaċja tagħhom ma ġewx evalwati klinikament.
Therefore, virological response should be closely monitored.
Għalhekk, ir - rispons viroloġiku għandu jiġi mmonitorjat mill- qrib.
Exacerbations of hepatitis: spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by transient increases in serum ALT.
Taħrix ta ’ l- epatite: taħrix spontanju ta ’ epatite B kronika huwa relattivament komuni u huwa kkaratterizzat bi żjidiet temporanji fl- ALT fis- serum.
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
Among entecavir-treated patients on-treatment exacerbations had a median time of onset of 4-5 weeks.
Fost pazjenti ttrattati b’ entecavir, it- taħrix waqt it- trattament, bħala medja beda 4- 5 ġimgħat wara.
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 ġeneralment m’ humiex akkumpanjati b’ żjieda fil- konċentrazzjonijiet tal- bilirubin fis- serum jew b’ di - kumpensazzjoni epatika.
Patients with cirrhosis 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.
3 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.
Post-treatment exacerbations are usually associated with rising HBV DNA, and the majority appears to be self-limited.
Taħrix wara t- trattament huwa ġeneralment assoċjat ma ’ żjieda fl- ammont ta ’ DNA ta ’ HBV, u jidher li l - maġġoranza tagħhom jillimitaw lilhom infushom.
However, severe exacerbations, including fatalities, have been reported.
Madankollu ġew irrapportati wkoll, taħrix gravi, inkluż fatalitjiet.
Among entecavir-treated nucleoside naive patients, post-treatment exacerbations had a median time to onset of 23-24 weeks, and most were reported in HBeAg negative patients (see section 4.8).
Fost pazjenti li huma nucleoside naïve ittrattati b’ entecavir, it- taħrix ta ’ wara t- trattament, bħala medja beda 23- 24 ġimgħa wara, u ħafna minn dan it- taħrix ġie rrapportat f’ pazjenti negattivi għal HBeAg (ara sezzjoni 4. 8).
Hepatic function should be monitored at repeated intervals with both clinical and laboratory follow-up for at least 6 months after discontinuation of hepatitis B therapy.
Il- funzjoni epatika trid tiġi mmonitorjata f’ intervalli ripetuti b’ follow up kemm kliniku kif ukoll mil- laboratorju għal mill- inqas 6 xhur wara t- twaqqif tat- terapija għal epatite B.
If appropriate, resumption of hepatitis B therapy may be warranted.
Jekk ikun applikabbli, jista ’ jkun hemm ġustifikazzjoni biex it- terapija għall- epatite B tinbeda mill- ġdid.
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 ġew osservati 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 fuq 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.
Patients experiencing signs of hepatic insufficiency during or post-treatment should be monitored more frequently as appropriate.
Pazjenti li jesperjenzaw sinjali ta ’ insuffiċjenza epatika waqt jew wara t- trattament, għandhom jiġu immonitorjati b’ iktar frekwenza skond il- ħtieġa.
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 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.
As entecavir is a nucleoside analogue, this risk cannot be excluded.
Minħabba li entecavir huwa nucleoside analogue, dan ir- riskju ma jistax jiġi eskluż.
Treatment with nucleoside analogues should be discontinued when rapidly elevating aminotransferase levels, progressive hepatomegaly or metabolic/ lactic acidosis of unknown aetiology occur.
Trattament b’ nucleoside analogues irid jitwaqqaf meta jkun hemm livelli ta ’ aminotransferase li jkunu qed jogħlew b’ rata mgħaġġla, epatomegalija progressiva jew aċidożi metabolika/ lattika ta ’ etjoloġija mhux magħrufa.
Benign digestive symptoms, such as nausea, vomiting and abdominal pain, might be indicative of lactic acidosis development.
Sintomi diġestivi beninnji, bħal dardir, rimettar u uġigħ addominali, jistgħu jindikaw l- iżvilupp ta ’ aċidożi lattika.
Severe cases, sometimes with fatal outcome, were associated with pancreatitis, liver failure/ hepatic steatosis, renal failure and higher levels of serum lactate.
Każijiet severi, xi kultant b’ riżultati fatali, kienu assoċjati ma ’ pankreatite, indeboliment tal- fwied/ steatożi epatika, indeboliment tal- kliewi u livelli ogħla ta ’ lactate fis- serum.
Caution should be exercised when prescribing nucleoside analogues to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease.
Għandha tingħata attenzjoni kbira meta tkun se ssir riċetta għal nucleoside analogues lil kull pazjent (partikolarment għal nisa ħoxnin ħafna) b’ epatomegalija, epatite jew b’ fatturi oħra magħrufin li jistgħu jkunu ta ’ riskju għall- mard tal- fwied.
These patients should be followed closely.
Dawn il- pazjenti jeħtieġu jiġu segwiti bir- reqqa.
To differentiate between elevations in aminotransferases due to response to treatment and increases potentially related to lactic acidosis, physicians should ensure that changes in ALT are associated with improvements in other laboratory markers of chronic hepatitis B.
Biex jagħmlu differenza bejn elevazzjonijiet f’ aminotransferases minħabba rispons għat- trattament u żjidiet potenzjalment relatati ma ’ aċidożi lattika, it- tobba jridu jiżguraw li bidliet fl- ALT huma assoċjati ma ’ titjib f’ markers laboratorji oħra ta ’ l- epatite B kronika.
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).
In a small percentage of lamivudine-refractory patients, ETVr substitutions at residues rtT184, rtS202 or rtM250 were present at baseline.
F’ perċentwal żgħir ta ’ pazjenti refrattarji għal lamivudine, sostituzzjonijiet ETVr f’ residwi rtT184, rtS202 jew rtM250 kienu preżenti fil- linja bażi.
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.
The cumulative probability of emerging genotypic entecavir resistance after 1, 2, 3, 4 and 5 years treatment in the lamivudine-refractory studies was 6%, 15%, 36%, 47% and 51%, respectively.
Il- probabbiltà kumulattiva ta ’ reżistenza ġenotipika ġdida għal entecavir wara 1, 2, 3, 4 u 5 snin ta ’ kura fi studji dwar pazjenti li kienu refrattarji għal lamivudine kienet ta ’ 6%, 15%, 36%, 47% u 51%, rispettivament.
Virological response should be frequently monitored in the lamivudine-refractory population and appropriate resistance testing should be performed.
Ir- rispons viroloġiku għandu jiġi mmonitorjat b’ mod frekwenti fil- popolazzjoni li hi refrattarja għal lamivudine, u għandu jsir ittestjar adattat dwar ir- reżistenza.
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).
F’ pazjenti b’ rispons viroloġiku li jkun inqas mill- aħjar 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.
4 Riċevituri ta ’ trapjant tal- fwied: hemm ftit tagħrif fuq l- effikaċja u s- sigurtà ta ’ entecavir f’ riċevituri ta ’ trapjant tal- fwied.
Renal function should be carefully evaluated before and during entecavir therapy in liver transplant recipients receiving cyclosporine or tacrolimus (see section 5.2).
Il- funzjoni tal- kliewi trid tiġi evalwata b’ attenzjoni kbira qabel u waqt it- terapija b’ entecavir f’ riċevituri ta ’ trapjant tal- fwied li jkunu qed jirċievu cyclosporine jew tacrolimus (ara sezzjoni 5. 2).
Co-infection with hepatitis C or D: there are no data on the efficacy of entecavir in patients co-infected with hepatitis C or D virus.
Infezzjoni fl- istess ħin bl- epatite Ċ jew D: m’ hemmx tagħrif fuq l- effikaċja ta ’ entecavir f’ pazjenti infettati fl- istess ħin bil- virus ta ’ l- epatite Ċ jew D.
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
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.
Emergence of HIV resistance has been observed when entecavir was used to treat chronic hepatitis B infection in patients with HIV infection not receiving highly active antiretroviral therapy (HAART) (see section 5.1).
Ġie osservat li tfaċċat reżistenza ta ’ l- HIV meta entecavir intuża għall- kura ta ’ infezzjoni kronika ta ’ l- epatite B f’ pazjenti b’ infezzjoni ta ’ l- HIV li ma kinux qegħdin jingħataw kura antiretrovirali effettiva ħafna (HAART) (ara sezzjoni 5. 1).
Therefore, therapy with entecavir should not be used for HIV/ HBV co-infected patients who are not receiving HAART.
Għalhekk, m’ għandhiex tintuża kura b’ entecavir għal pazjenti infettati fl- istess ħin bl- HIV/ HBV li ma jkunux qegħdin jingħataw HAART (Terapija Antiretrotrivali Attiva Ħafna).
Entecavir has not been studied as a treatment for HIV infection and is not recommended for this use.
Entecavir ma ġiex studjat bħala kura għal infezzjoni bl- HIV u mhux irrakkomandat biex jintuża għalhekk.
HIV/ HBV co-infected patients receiving concomitant antiretroviral therapy: entecavir has been studied in 68 adults with HIV/ HBV co-infection receiving a lamivudine-containing HAART regimen (see section 5.1).
Pazjenti ko- infettati bl- HIV/ HBV li jkunu qed jingħataw terapija antiretrovirali fl- istess ħin: entecavir ġie studjat fi 68 adult b’ infezzjoni fl- istess ħin ta ’ l- HIV/ HBV li kienu qegħdin jingħataw reġim HAART li kien fih lamivudine (ara sezzjoni 5. 1).
No data are available on the efficacy of entecavir in HBeAg-negative patients co-infected with HIV.
M’ hemmx tagħrif fuq l- effikaċja ta ’ entecavir f’ pazjenti li rriżultaw negattivi għal HBeAg li huma infettati wkoll bl- 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).
General: patients should be advised that therapy with entecavir has not been proven to reduce the risk of transmission of HBV and therefore appropriate precautions should still be taken.
Ġenerali: il- pazjenti jridu jiġu avżati li ma ngħatat l- ebda prova li t- terapija b’ entecavir tnaqqas ir - riskju ta ’ trasmissjoni ta ’ HBV u għalhekk xorta waħda għandhom jittieħdu l- prekawzjonijiet meħtieġa.
Lactose: this medicinal product contains 120.5 mg of lactose in each 0.5 mg daily dose.
Lactose: dan il- prodott mediċinali fih 120. 5 mg ta ’ lactose f’ kull doża ta ’ kuljum ta ’ 0. 5 mg.
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 tal- galactose, Lapp lactase deficiency jew nuqqas ta ’ assorbiment ta 'glucose- galactose m' għandhomx jieħdu din il- mediċina.
A lactose-free Baraclude oral solution is available for these individuals.
Hemm soluzzjoni orali għal dawn l- individwi, Baraclude mingħajr lactose.
Since entecavir is predominantly eliminated by the kidney (see section 5.2), coadministration with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of either medicinal product.
Minħabba li entecavir jiġi eliminat l- aktar mill- kliewi (ara sezzjoni 5. 2), l- għoti tal- prodott ma ’ mediċinali oħra li jnaqqsu l- funzjoni renali jew li jikkompetu għal sekrezzjoni tubulari attiva jista ’ jgħolli l- konċentrazzjoni fis- serum ta ’ wieħed mill- prodotti mediċinali.
Apart from lamivudine, adefovir dipivoxil and tenofovir disoproxil fumarate, the effects of coadministration of entecavir with medicinal products that are excreted renally or affect renal function have not been evaluated.
Barra lamivudine, adefovir dipivoxil u tenofovir disoproxil fumarate, l- effetti ta ’ l- għoti ta ’ entecavir ma ’ prodotti mediċinali oħra li joħorġu mill- kliewi jew ma ’ xi prodotti li jaffettwaw il- funzjoni renali ma ġewx evalwati.
Patients should be monitored closely for adverse reactions when entecavir is coadministered with such medicinal products.
Il- pazjenti jridu jiġu mmonitorjati mill- qrib għal effetti negattivi meta entecavir jittieħed flimkien ma ’ prodotti mediċinali bħal dawn.
No pharmacokinetic interactions between entecavir and lamivudine, adefovir or tenofovir were observed.
Ma ġiet osservata ebda interazzjoni farmakokinetika bejn entecavir u lamivudine, adefovir jew tenofovir.
Entecavir is not a substrate, an inducer or an inhibitor of cytochrome P450 (CYP450) enzymes (see section 5.2).
Entecavir m’ huwiex sottostrat, inducer jew impeditur ta ’ enżimi ta ’ cytochrome P450 (CYP450) (ara sezzjoni 5. 2).
Therefore CYP450 mediated drug interactions are unlikely to occur with entecavir.
Għalhekk interazzjonijiet bejn id- drogi b’ CYP450 bħala medjatur, mhux probabbli li jseħħu b’ entecavir.
There are no adequate data from the use of entecavir in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ entecavir waqt it- tqala.
Studies in animals have shown reproductive toxicity at high doses (see section 5.3).
Studji fuq bhejjem urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 5. 3).
Baraclude should not be used during pregnancy unless clearly necessary.
Baraclude m’ għandux jintuża waqt it- tqala ħlief meta hemm bżonn speċifiku.
Given that the potential risks to the developing foetus are unknown, women of child-bearing potential should use effective contraception.
5 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.
There are no data on the effect of entecavir on transmission of HBV from mother to newborn infant.
M’ hemmx tagħrif dwar l- effett ta ’ entecavir fuq it- trasmissjoni ta ’ HBV mingħand l- omm għat- tarbija tagħha li tkun għadha kif twieldet.
Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.
Għalhekk għandhom jintużaw interventi xierqa biex it- tarbija li tkun għadha kif twieldet ma tiħux l- HBV.
It is unknown whether entecavir is excreted in human breast milk.
M’ huwiex magħruf jekk entecavir joħroġx fil- ħalib tas- sider ta ’ l- omm.
Animal studies have shown excretion of entecavir in breast milk.
Studji fl- annimali wrew li entecavir jgħaddi għall- ħalib tas- sider.
Breastfeeding is not recommended during treatment with Baraclude.
Għaldaqstant it- treddigħ m’ huwiex irrakkomandat waqt trattament bi Baraclude.
No effect on such activities is expected based on the pharmacodynamic profile of entecavir.
L- ebda effett m’ huwa mistenni fuq attivitajiet bħal dawn fuq il- bażi tal- profil farmakodinamiku ta ’ entecavir.
Dizziness, fatigue and somnolence are common side effects which may impair the ability to drive and use machines.
Sturdament, għeja u ngħas mhux f’ waqtu huma effetti sekondarji komuni, u dawn jistgħu jfixklu l- ħila biex issuq u tħaddem magni.
Assessment of adverse reactions is based on four clinical studies in which 1,720 patients with chronic hepatitis B infection received double-blind treatment with entecavir 0.5 mg/ day (n = 679), entecavir 1 mg/ day (n = 183), or lamivudine (n = 858) for up to 107 weeks.
Il- valutazzjoni ta ’ l- effetti negattivi hija bbażata fuq erba ’ studji kliniċi, fejn 1, 720 pazjent b’ infezzjoni kronika ta ’ l- epatite B irċevew trattament double blind b’ 0. 5mg/ jum (n= 679) ta ’ entecavir, b’ 1mg/ jum (n= 183) ta ’ entecavir jew lamivudine (n= 858) sa 107 ġimgħat.
The safety profiles of entecavir and lamivudine, including laboratory test abnormalities, were comparable in these studies.
Il- profili tas- sigurtà ta ’ entecavir u lamivudine, inkluż anomaliji tat- testijiet tal- laboratorju, kienu komparabbli f’ dawn l- istudji.
The most common adverse reactions of any severity with at least a possible relation to entecavir were headache (9%), fatigue (6%), dizziness (4%) and nausea (3%).
L- iktar effetti avversi komuni ta ’ kull gravità, li ta ’ l- inqas jista ’ jkollhom il- possibbilità ta ’ relazzjoni ma ’ entecavir kienu l- uġigħ ta ’ ras (9%), għeja (6%), sturdament (4%) u dardir (3%).
Adverse reactions considered at least possibly related to treatment with entecavir are listed by body system organ class.
Reazzjonijiet avversi meqjusin li ta ’ l- inqas jistgħu jkunu relatati ma ’ entecavir huma elenkati skond is- sistema ta ’ klassifika ta ’ l- organi.
Frequency is defined as very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10).
Il- frekwenza hija ddefinita bħala komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100, < 1/ 10).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is - serjetà tagħhom.
Experience in nucleoside naive patients (HBeAg positive and negative):
Esperjenza f’ pazjenti li huma nucleoside naïve (pożittivi u negattivi għal HBeAg):
The safety profile is based on treatment exposure to entecavir 0.5 mg once daily for a median of 53 weeks.
Il- profil tas- sigurtà huwa bbażat fuq studju ta ’ pazjenti li ħadu entacavir 0. 5 mg darba kuljum għal medja ta ’ 53 ġimgħa.
Nervous system disorders:
komuni: uġigħ ta ’ ras, sturdament, ngħas żejjed Disturbi fis- sistema nervuża:
Gastrointestinal disorders:
komuni: rimettar, dijarea, dardir, dispepsja Disturbi gastro- intestinali:
General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta 'komuni: għeja mnejn jingħata:
Psychiatric disorders:
komuni: nuqqas ta ’ rqad Disturbi psikjatriċi:
Laboratory test abnormalities:
Anomaliji fit- testijiet tal- laboratorju:
2% of patients had ALT elevations both > 10 times upper limit of the normal range (ULN) and > 2 times baseline, 5% had ALT elevations > 3 times baseline, and< 1% had ALT elevations > 2 times baseline together with total bilirubin > 2 times ULN and> 2 times baseline.
2% tal- pazjenti kellhom livelli għoljin ta ’ ALT kemm > 10 darbiet il- limitu ta ’ fuq tal- medda normali (ULN) kif ukoll > darbtejn il- linja bażi, 5% kellhom livelli għoljin ta ’ ALT li kienu > 3 darbiet ogħla mil- linja bażi, u < 1% kellhom livelli għoljin ta ’ ALT > darbtejn il- linja bażi flimkien ma ’ total ta ’ bilirubin ta ’ > darbtejn l- ULN u > darbtejn il- linja bażi.
Albumin levels < 2.5 g/ dl occurred in < 1% of patients, amylase levels > 3 times basel ine in 2%, lipase levels > 3 times baseline in 11% and platelets < 50,000/mm3 in < 1%.
Livelli ta ’ l- albumina ta ’ < 2. 5 g/ dl instabu f ’ < 1% tal- pazjenti, livelli ta ’ amylase > 3 darbiet iktar mil - linja bażi fi 2%, livelli ta ’ lipase > 3 drabi l- linja bażi fi 11% u platelets < 50, 000/ mm3 fi < 1%.
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.
Experience in lamivudine-refractory patients:
6 Esperjenza f’ pazjenti li huma refrattarji għal lamivudine:
The safety profile is based on treatment exposure to entecavir 1 mg once daily for a median of 69 weeks.
Il- profil tas- sigurtà huwa bbażat fuq studju ta ’ pazjenti li ħadu 1 mg ta ’ entacavir darba kuljum għal medja ta ’ 69 ġimgħa.
very common: headache common: dizziness, somnolence
komuni ħafna: uġigħ ta 'ras Disturbi fis- sistema nervuża: komuni: sturdament, ngħas żejjed
2% of patients had ALT elevations both > 10 times ULN and > 2 times baseline, 4% had ALT elevations > 3 times baseline, and< 1% had ALT elevations > 2 times baseline together with total bilirubin > 2 times ULN and> 2 times baseline.
2% tal- pazjenti kellhom livelli għoljin ta ’ ALT kemm > 10 darbiet l- ULN kif ukoll > darbtejn il- linja bażi, 4% kellhom livelli għoljin ta ’ ALT li kienu > 3 darbiet il- linja bażi, u < 1% kellhom livelli għoljin ta ’ ALT > darbtejn il- linja bażi flimkien ma ’ bilirubin totali ta ’ > darbtejn l- ULN u > darbtejn il- linja bażi.
Amylase levels > 3 times baseline occurred in 2% of patients, lipase levels > 3 times baseline in 18% and platelets < 50,000/ mm3 in < 1%.
Livelli ta ’ amylase > 3 darbiet il- linja bażi fi 2% tal- pazjenti, livelli ta ’ lipase > 3 darbiet il- linja bażi fi 18% u platelets < 50, 000/ mm3 f ’ < 1%.
6 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.
Exacerbations during treatment: in studies with nucleoside naive patients, on treatment ALT elevations > 10 times ULN and > 2 times baseline occurred in 2% of entecavir treated patients vs 4% of lamivudine treated patients.
Taħrix waqt it- trattament: fi studji fuq pazjenti nucleoside naïve, seħħew żjidiet fil- livelli ta ’ ALT waqt it- trattament b ’ > 10 darbiet il- ULN u > darbtejn iktar il- linja bażi f’ pazjenti ttrattati b’ entecavir meta mqabbla ma ’ 4% tal- pazjenti ttrattati b’ lamivudine.
In studies with lamivudine-refractory patients, on treatment ALT elevations > 10 times ULN and > 2 times baseline occurred in 2% of entecavir treated patients vs 11% of lamivudine treated patients.
Fi studji fuq pazjenti refrattarji għal lamivudine, seħħew żjidiet fil- livelli ta ’ ALT waqt it- trattament ta ’ > 10 darbiet l- ULN u > darbtejn il - linja bażi fi 2% tal- pazjenti trattati b’ entecavir meta mqabbla ma ’ 11% tal- pazjenti trattati b’ lamivudine.
Among entecavir-treated patients, on-treatment ALT elevations had a median time to onset of 4-5 weeks, generally resolved with continued treatment, and, in a majority of cases, were associated with a ≥ 2 log10/ ml reduction in viral load that preceded or coincided with the ALT elevation.
Fost il- pazjenti ttrattati b’ entecavir, iż- żjidiet fil- livelli ta ’ ALT waqt it- trattament feġġew wara medja ta ’ 4- 5 ġimgħat mill- bidu tat- trattament, u ġeneralment dawn irriżolvew ruħhom meta komplew it- trattament, u, fil- maġġoranza tal- każijiet, kienu assoċjati ma ’ tnaqqis ta ’ ≥ 2log10/ ml fil- viral load li ppreċediet jew li ħabtet maż- żjieda fl- ALT.
Periodic monitoring of hepatic function is recommended during treatment.
Monitoraġġ perjodiku tal- funzjoni tal - fwied huwa rrakkomandat waqt it- trattament.
Exacerbations after discontinuation of treatment: acute exacerbations of hepatitis have been reported in patients who have discontinued anti-hepatitis B virus therapy, including therapy with entecavir (see section 4.4).
Taħrix wara li jitwaqqaf it- trattament: ġie rrapportat taħrix akut ta ’ epatite f’ pazjenti li waqqfu t - terapija kontra l- virus ta ’ l- epatite B, inkluż terapija b’ entecavir (ara sezzjoni 4. 4).
In studies in nucleoside-naive patients, 6% of entecavir-treated patients and 10% of lamivudine-treated patients experienced ALT elevations (> 10 times ULN and > 2 times reference [minimum of baseline or last end-of-dosing measurement]) during post-treatment follow-up.
Fi studji f’ pazjenti li huma nucleoside naïve, 6% tal- pazjenti ttrattati b’ entecavir u 10% tal- pazjenti ttrattati b’ lamivudine urew żjidiet fl- ALT (> 10 darbiet l- ULN u > darbtejn ir- referenza [il- minimu tal- linja bażi jew l- aħħar kejl fl- aħħar tad- dożi]) waqt follow- up ta ’ wara t- trattament.
Among entecavir-treated nucleoside-naive patients, ALT elevations had a median time to onset of 23-24 weeks, and 86% (24/ 28) of ALT elevations occurred in HBeAg negative patients.
Fost pazjenti ttrattati b’ entecavir li huma nucleoside naïve, żjidiet fl- ALT feġġew 23- 24 ġimgħa wara li waqqfu t- trattament, u 86% (24/ 28) taż - żjidiet fl- ALT seħħew f’ pazjenti negattivi għal HBeAg.
In studies in lamivudine-refractory patients, with only limited numbers of patients being followed up, 11% of entecavir-treated patients and no lamivudine-treated patients developed ALT elevations during post- treatment follow-up.
Fi studji f’ pazjenti refrattarji għal lamivudine, b’ numru limitat ta ’ pazjenti li kienu qegħdin jiġu osservati, 11% tal- pazjenti ttrattati b’ entecavir u ebda pazjenti ttrattat b’ lamivudine ma żviluppaw żjidiet fl- ALT waqt follow- up li sar wara t- trattament.
In the clinical trials entecavir treatment was discontinued if patients achieved a prespecified response.
Fil- provi kliniċi, it- trattament b’ entecavir twaqqaf jekk il- pazjenti laħqu effett pożittiv speċifikat minn qabel.
If treatment is discontinued without regard to treatment response, the rate of post-treatment ALT flares could be higher.
Jekk it- trattament jitwaqqaf mingħajr ma jingħata kas ta ’ dan l- effett pożittiv, ir- rata tal- flares ta ’ ALT ta ’ wara t- trattament tista ’ tkun ikbar.
Experience in patients co-infected with HIV: the safety profile of entecavir in a limited number of HIV/ HBV co-infected patients on lamivudine-containing HAART (highly active antiretroviral therapy) regimens was similar to the safety profile in monoinfected HBV patients (see section 4.4).
Esperjenza f’ pazjenti infettati fl- istess ħin bl- HIV: il- profil tas- sigurtà ta’ entecavir f’ numru limitat ta ’ pazjenti infettati bl- HIV/ HBV li kienu fuq lamivudine bħala parti mit- terapija HAART (terapija antiretrovirali attiva ħafna), kien simili għall- profil tas- sigurtà ta ’ dawk infettati bl- HBV biss (ara sezzjoni 4. 4).
Gender/ age: there was no apparent difference in the safety profile of entecavir with respect to gender (≈ 25% women in the clinical trials) or age (≈ 5% of patients > 65 years of age).
Ġeneru/ età: ma kienx hemm differenza apparenti fil- profil tas- sigurtà ta ’ entecavir fir- rigward tal - ġeneru (≈25% tan- nisa fil- provi kliniċi) jew età (≈5% tal- pazjenti > 65 sena).
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.
7 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.
Postmarketing experience: in addition to the adverse drug reactions identified from clinical trials, the following adverse reaction has been identified during post-approval use of entecavir.
Esperjenza ta ’ wara t- tqegħid fis- suq: barra mir- reazzjonijiet avversi tal- mediċina identifikati minn provi kliniċi, ir- reazzjoni avversa li ġejja ġiet identifikata matul użu ta ’ wara t- tqegħid fis- suq ta ’ entecavir.
Skin and subcutaneous tissue disorders:
frekwenza mhix magħrufa: raxx Disturbi tal- ġilda u tat- tessuti ta ’ taħt il- ġilda:
frequency not known: rash
4. 9 Doża eċċessiva
Healthy subjects who received up to 20 mg/ day for up to 14 days, and single doses up to 40 mg had no unexpected adverse reactions.
Pazjenti b’ saħħithom li rċevew sa 20 mg/ jum sa 14- il ġurnata, u dożi waħdiet sa 40 mg, ma kellhomx reazzjonijiet avversi mhux mistennija.
If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.
Jekk tittieħed doża eċċessiva, il- pazjent irid jiġi mmonitorjat għal evidenza ta ’ tossiċità u għandu jingħata trattament t’ appoġġ bħas- soltu, skond il- bżonn.
Pharmacotherapeutic group: nucleoside and nucleotide reverse transcriptase inhibitors
Kategorija farmakoterapewtika: nucleoside u nucleotide reverse transcriptase inhibitors Kodiċi ATC:
Mechanism of action: entecavir, a guanosine nucleoside analogue with activity against HBV polymerase, is efficiently phosphorylated to the active triphosphate (TP) form, which has an intracellular half-life of 15 hours.
Kif jaħdem: entecavir, analogue ta ’ guanosine nucleoside b’ attività kontra polymerase tal- HBV, huwa fosforilatat b’ mod effiċjenti mal- forma attiva ta ’ triphosphat (TP), li għandha half- life ta ’ 15- il siegħa.
By competing with the natural substrate deoxyguanosine TP, entecavir-TP functionally inhibits the 3 activities of the viral polymerase:
Billi jikkompeti mas- sottostrat naturali deoxyguanosine TP, entecavir TP jaħdem billi ixejjen it- tlett attivitajiet tal- polymerase virali:
(1) priming of the HBV polymerase, (2) reverse transcription of the negative strand DNA from the pregenomic messenger RNA, and (3) synthesis of the positive strand HBV DNA.
(1) priming ta ’ polymerase ta ’ HBV, (2) traskrizzjoni bil- maqlub ta ’ l- istrand negattiv tad- DNA mill- messaġġier pregenomiku RNA, u (3) sintesi ta ’ l- istrand pożittiv tad - DNA tal- HBV.
The entecavir-TP Ki for HBV DNA polymerase is 0.0012 μ M.
Il- Ki ta ’ entecavir- TP għal polymerase tad- DNA ta ’ HBV huwa 0. 0012 µM.
Entecavir-TP is a weak inhibitor of cellular DNA polymerases α, β, and δ with Ki values of 18 to 40 µM.
Entecavir - TP ifixkel polymerases tad- DNA α, β u δ fiċ- ċelloli b’ valuri ta ’ Ki ta ’ 18 sa 40 µM.
In addition, high exposures of entecavir had no relevant adverse effects on γ polymerase or mitochondrial DNA synthesis in HepG2 cells (Ki > 160 µM).
Barra minn hekk, doża qawwija ta ’ entecavir ma kellha l- ebda effett negattiv fuq il- polymerase ta ’ γ jew is- sintesi tad - DNA fil- mitochondrion f’ ċelloli HepG2 (Ki > 160 µM).
Antiviral activity: entecavir inhibited HBV DNA synthesis (50% reduction, EC50) at a concentration of 0.004 µM in human HepG2 cells transfected with wild-type HBV.
Attività antivirali: entecavir impedixxa s- sintesi ta ’ DNA ta ’ HBV (tnaqqis ta ’ 50%, EC50) f’ konċentrazzjoni ta ’ 0. 004 µM f’ ċelloli HepG2 umani transinfettati b’ HBV wild- type.
The median EC50 value for entecavir against LVDr HBV (rtL180M and rtM204V) was 0.026 µM (range 0.010-0.059 µM).
Il- valur medju ta ’ EC50 għal entecavir kontra LVDr HBV (rtL180M u rtM204V) kien ta ’ 0. 026 µM (medda ta ’ 0. 010- 0. 059 µM).
Recombinant viruses encoding adefovir-resistant substitutions at either rtN236T or rtA181V remained fully susceptible to entecavir.
Virusijiet rikombinanti li kien fihom sostituzzjonijiet reżistenti għal adefovir jew f’ rtN236T jew f’ rtA181V baqgħu suxxetibbli għal kollox għal entecavir.
An analysis of the inhibitory activity of entecavir against a panel of laboratory and clinical HIV-1 isolates using a variety of cells and assay conditions yielded EC50 values ranging from 0.026 to > 10 µM; the lower EC50 values were observed when decreased levels of virus were used in the assay.
Analiżi ta ’ l- attività inibitorja ta ’ entecavir kontra gruppi ta’ viruses HIV- 1 iżolati minn pazjenti u minn kulturi fil- laboratorju li jużaw varjetà ta ’ ċelloli u kundizzjonijiet ta ’ assaġġi taw valuri EC50 li varjaw minn 0. 026 sa > 10 µM; il- valuri EC50 l- baxxi ġew osservati meta ntużaw livelli mnaqqsa tal- virus fl - assaġġ.
In cell culture, entecavir selected for an M184I substitution at micromolar concentrations, confirming inhibitory pressure at high entecavir concentrations.
F’ kultura ta ’ ċelloli, entecavir magħżul għax kellu sostituzzjoni ta ’ M184I f’ konċentrazzjonijiet mikromolari, ġiet ikkonfermata pressjoni inibitorja f’ konċentrazzjonijiet għolja ta ’ entecavir.
HIV variants containing the M184V substitution showed loss of susceptibility to entecavir (see section 4.4).
Varjanti ta ’ l- HIV li kien fihom is- sostituzzjoni ta ’ M184V tilfu s- suxxettibilità għal entecavir (ara sezzjoni 4. 4).
In HBV combination assays in cell culture, abacavir, didanosine, lamivudine, stavudine, tenofovir or zidovudine were not antagonistic to the anti-HBV activity of entecavir over a wide range of concentrations.
F’ assaġġi ta ’ kombinazzjoni ta ’ HBV f’ kultura ta ’ ċelloli, abacavir, didanosine, lamivudine, stavudine, tenefovir u zidovudine ma kienux antagonistiċi għall- attività ta ’ entecavir kontra HBV fuq medda wiesgħa ta ’ konċentrazzjonijiet.
In HIV antiviral assays, entecavir at micromolar concentrations was not antagonistic to the anti-HIV activity in cell culture of these six NRTIs or emtricitabine.
F’ assaġġi antivirali ta ’ l- HIV, entecavir f’ konċentrazzjonijiet mikromolari ma kienx antagonistiku għall- attività kontra l- HIV f’ kultura ta ’ ċelloli ta ’ dawn is- sitt NRTI jew emtricitabine.
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.
8 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.
Incorporation of additional ETVr amino acid changes rtT184, rtS202 or rtM250 decreases entecavir susceptibility in cell culture.
L- inkorporazzjoni ta ’ aċidu amminiku addizzjonali ETVr tbiddel l- rtT184, rtS202 jew l- rtM250 tnaqqas is- suxxettibilità għal entecavir f’ kultura ta ’ ċelloli.
Substitutions observed in clinical isolates (rtT184A, C, F, G, I, L, M or S; rtS202 C, G or I; and/ or rtM250I, L or V) further decreased entecavir susceptibility 16- to 741-fold relative to wild-type virus.
Is- sostituzzjonijiet osservati fl - iżolati kliniċi (rtT184A, C, F, G, I, L, M jew S; rtS202 C, G jew I; u/ jew rtM250I, L jew V) komplew inaqqsu s- suxxettibilità għal entecavir bejn 16 u 741 darba relattiv għall- virus wild- type.
The ETVr substitutions at residues rtT184, rtS202 and rtM250 alone have only a modest effect on entecavir susceptibility, and have not been observed in the absence of LVDr substitutions in more than 1000 patient samples sequenced.
Is - sostituzzjonijiet ETVr fir- residwi rtT184, rtS202 u rtM250 weħidhom għandhom biss effett modest fuq is- suxxettibilità għal entecavir, u ma ġewx osservati fin- nuqqas ta ’ sostituzzjonijiet LVDr f’ aktar minn 1000 pazjent studjati.
Resistance is mediated by reduced inhibitor binding to the altered HBV reverse transcriptase, and resistant HBV exhibits reduced replication capacity in cell culture.
Ir- reżistenza hija medjata minn irbit anqas ta ’ l- inibitur mar- reverse transcriptase HBV mibdul, u l- HBV reżistenti juri kapaċità anqas li jimmultiplika f’ kultura ta ’ ċelloli.
Clinical experience: the demonstration of benefit is based on histological, virological, biochemical, and serological responses after 48 weeks of treatment in active-controlled clinical trials of 1,633 adults with chronic hepatitis B infection and evidence of viral replication.
Esperjenza Klinika: it- turija tal- benefiċċju hija bbażata fuq istoloġija, viroloġija, bijokimika u effetti seroloġiċi wara 48 ġimgħa ta ’ trattament fi provi kliniċi attivi kkontrollati ta ’ 1, 633 adult b’ epatite B kronika u b’ evidenza ta ’ replikazzjoni virali.
In all studies, histological improvement was defined as a ≥ 2-point decrease in Knodell necro- inflammatory score from baseline with no worsening of the Knodell fibrosis score.
Fl- istudji kollha, titjib istoloġiku ġie definit bħala tnaqqis ta ’ ≥ 2 punti f’ Knodell necro- inflammatory score mil- linja bażi mingħajr ma ’ l- Knodell fibrosis score imur għall- agħar.
Responses for patients with baseline Knodell Fibrosis Scores of 4 (cirrhosis) were comparable to overall responses on all efficacy outcome measures (all patients had compensated liver disease).
Effetti fuq pazjenti b’ linja bażi ta ’ 4 fuq il- Knodell Fibrosis Score (ċirrożi) kienu komparabbli mal- effett totali fuq il- miżuri kollha ta ’ l- effikaċja totali (il- pazjenti kollha kellhom mard tal- fwied ikkumpensat).
High baseline Knodell necroinflammatory scores (> 10) were associated with greater histological improvement in nucleoside- naive patients.
Linji bażi għoljin ta ’ Knodell necro- nflammatory scores (> 10) ġew assoċjati ma ’ titjib ikbar fl- istoloġija f’ pazjenti li huma nucleoside naïve.
Baseline ALT levels ≥ 2 x ULN and baseline HBV DNA ≤ 9.0 log10 copies/ ml were both associated with higher rates of virologic response (Week 48 HBV DNA < 400 copies/ ml) in nucleoside-naive HBeAg-positive patients.
Livelli ta ’ ALT ta ’ linja bażi ta ’ ≥ 2 x l- ULN u DNA ta ’ HBV ta ’ linja bażi ≤ 9. 0 log10 kopji/ ml kienu t- tnejn li huma assoċjati ma ’ rati ogħla ta ’ titjib viroloġiku (Ġimgħa 48 DNA ta ’ HBV < 400 kopja/ ml) f’ pazjenti li huma nucleoside naïve u pożittivi għal HBeAg.
Regardless of baseline characteristics, the majority of patients showed histological and virological responses to treatment.
Mingħajr ma ngħata kas tal- karatterisitiċi tal- linja bażi, il- maġġoranza tal- pazjenti wrew reazzjonijiet istoloġiċi u viroloġiċi pożittivi għat- trattament.
Experience in nucleoside-naive patients with compensated liver disease:
Esperjenza f’ pazjenti li huma nucleoside naïve b’ mard tal- fwied ikkumpensat:
Results at 48 weeks of randomised, double blind studies comparing entecavir (ETV) to lamivudine
Ir- riżultati wara 48 ġimgħa ta ’ studji magħmulin b’ mod każwali, double blind li jqabblu entecavir (ETV) ma ’ lamivudine (LVD) f’ pazjenti pożittivi għal HBeAg (022) u f’ pazjenti negattivi għal HBeAg (027) jidhru fit- tabella.
Nucleoside Naive
Nucleoside Naive n
HBeAg Positive (study 022)
Pożittivi għal HBeAg (studju 022) ETV LVD 0. 5 mg 100 mg darba darba kuljum kuljum 314a 314a
once daily once daily once daily a a a
Negattivi għal HBeAg (studju 027) ETV LVD 0. 5 mg 100 mg darba darba kuljum kuljum 296a 287a
n Histological improvementb Ishak fibrosis score improvement Ishak fibrosis score worsening n Viral load reduction (log10 copies/ ml)c HBV DNA undetectable (< 300 copies/ ml by PCR)c
Titijib istoloġikub Ishak fibrosis score aħjar f’ Ishak fibrosis score agħar n Tnaqqis fil- viral load (log10 kopji/ ml) c DNA ta ’ HBV ma jistax jiġi osservat (< 300 kopja/ ml skond PCR) c
314 314 296 72%* 62% 70%* 39% 35% 36% 8% 10% 12% 354 355 325 -6.86* -5.39 -5.04* 67%* 36% 90%*
72% * 62% 39% 35% 8% 10% 354 355 - 6. 86 * - 5. 39 67% * 36%
287a 61% 38% 15% 313 -4.53 72%
70% * 61% 36% 38% 12% 15% 325 313 - 5. 04 * - 4. 53 90% * 72%
ALT normalisation (≤ 1 times ULN)
Normalizzazzjoni ta ’ l- ALT (≤ 1 x ULN)
68%* 60% 78%*
68% * 60%
HBeAg Seroconversion *p value vs lamivudine < 0.05 a
Sirokonversjoni ta ’ HBeAg * valur p vs lamivudine < 0. 05 a
patients with evaluable baseline histology (baseline Knodell Necroinflammatory Score ≥ 2) b a primary endpoint c Roche Cobas Amplicor PCR assay (LLOQ = 300 copies/ ml)
pazjenti b’ istoloġija ta ’ linja bażi li tista ’ tiġi evalwata (Knodell Necroinflammatory Score ta ’ linja bażi ≥ 2) b punt aħħari primarju c Roche Cobas Amplicor PCR assay (LLOQ = 300 kopja/ ml)
Experience in lamivudine-refractory patients:
9 Esperjenza f’ pazjenti li huma refrattarji għal lamivudine:
In a randomised, double-blind study in HBeAg positive lamivudine-refractory patients (026), with 85% of patients presenting LVDr mutations at baseline, patients receiving lamivudine at study entry either switched to entecavir 1 mg once daily, with neither a washout nor an overlap period (n = 141), or continued on lamivudine 100 mg once daily (n = 145).
Fi studju b’ mod każwali, double blind f’ pazjenti pożittivi għal HBeAg u refrattorji għal lamivudine (026), b’ 85% tal- pazjenti jippreżentaw mutazzjonijiet ta ’ LVDr fil- linja bażi, pazjenti li rċevew lamivudine malli daħlu fl- istudju jew qalbu għal 1mg ta ’ entecavir darba kuljum, mingħajr washout u mingħajr perijodu ta ’ overlap (n= 141), jew komplew b’ 100 mg ta ’ lamivudine darba kuljum (n= 145).
Results at 48 weeks are presented in the table.
Ir- riżultati wara 48 ġimgħa jidhru fit- tabella.
Lamivudine-refractory HBeAg positive (study 026) ETV 1.0 mg once daily LVD 100 mg once daily n
Rifrattorji għal Lamivudine Pożittivi għal HBeAg (studju 026)
116a
1. 0 mg darba kuljum
Histological improvementb Ishak fibrosis score improvement Ishak fibrosis score worsening n Viral load reduction (log10 copies/ ml)c HBV DNA undetectable (< 300 copies/ ml by PCR)c
n Titijib istoloġikub Ishak fibrosis score aħjar f’ Ishak fibrosis score agħar n Tnaqqis fil- viral load (log10 kopji/ ml) c DNA ta ’ HBV ma jistax jiġi osservat (< 300 kopja/ ml skond PCR) c
55%* 34%* 11% 141 -5.11* 19%*
124a 55% * 34% * 11% 141 - 5. 11 * 19% *
28% 16% 26% 145 -0.48 1%
116a 28% 16% 26% 145 - 0. 48 1%
patients with evaluable baseline histology (baseline Knodell Necroinflammatory Score ≥ 2) b a primary endpoint. c Roche Cobas Amplicor PCR assay (LLOQ = 300 copies/ ml)
pazjenti b’ istoloġija ta ’ linja bażi li tista ’ tiġi evalwata (Knodell Necroinflammatory Score ta ’ linja bażi ≥ 2) b punt aħħari primarju. c Roche Cobas Amplicor PCR assay (LLOQ = 300 kopja/ ml)
Results beyond 48 weeks of treatment:
Riżultati wara 48 ġimgħa ta ’ trattament:
Treatment was discontinued when prespecified response criteria were met either at 48 weeks or during the second year of treatment.
It- trattament twaqqaf meta ntlaħqu l- kriterji għall- effett li kienu speċifikati minn qabel jew fit - 48 ġimgħa jew waqt it- tieni sena tat- trattament.
Response criteria were HBV virological suppression (HBV DNA < 0.7 MEq/ ml by bDNA) and loss of HBeAg (in HBeAg positive patients) or ALT < 1.25 times ULN (in HBeAg negative patients).
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).
Patients in response were followed for an additional 24 weeks off-
Pazjenti b’ rispons pożittiv ġew segwiti għal 24 ġimgħa oħra bla trattament.
Patients who met virologic but not serologic or biochemical response criteria continued blinded treatment.
Pazjenti li ssodisfaw il- kriterji għar- rispons viroloġiku iżda mhux il - kriterji għar- rispons seroloġiku jew bijokimiku komplew bit- trattament blinded.
Patients who did not have a virologic response were offered alternative treatment.
Pazjenti li ma kellhomx rispons viroloġiku ġew offruti trattament alternattiv.
Nucleoside-naive:
Nucleoside- naive:
HBeAg positive (study 022): treatment with entecavir for up to 96 weeks (n = 354) resulted in cumulative response rates of 80% for HBV DNA < 300 copies/ ml by PCR, 87% for ALT normalisation, 31% for HBeAg seroconversion and 2% for HBsAg seroconversion (5% for HBsAg loss).
Pożittivi għal HBeAg (studju 022): trattament b’ entecavir sa 96 ġimgħa (n= 354) irriżulta f’ rati ta ’ titjib kumulattiv ta ’ 80% għal DNA ta ’ HBV < 300 kopja/ ml skond il- PCR, 87% għal normalizzazzjoni ta ’ ALT, 31% għal sirokonversjoni ta ’ HBeAg u 2% għal sirokonversjoni ta ’ HBsAg (5% għal tnaqqis ta ’ HBsAg).
For lamivudine (n = 355), cumulative response rates were 39% for HBV DNA < 300 copies/ ml by PCR, 79% for ALT normalisation, 26% for HBeAg seroconversion, and 2% for HBsAg seroconversion (3% for HBsAg loss).
Għal lamivudine (n= 355), ir- rati kienu 39% għal DNA ta ’ HBV < 300 kopja/ ml skond il- PCR, 79% għal normalizzazzjoni ta ’ l- ALT, 26% għal sirokonversjoni ta ’ HBeAg u 2% għal sirokonversjoni ta ’ HBsAg (3% għal tnaqqis ta ’ HBsAg).
At end of dosing, among patients who continued treatment beyond 52 weeks (median of 96 weeks), 81% of 243 entecavir-treated and 39% of 164 lamivudine-treated patients had HBV DNA < 300 copies/ ml by PCR while ALT normalisation (≤ 1 times ULN) occurred in 79% of entecavir- treated and 68% of lamivudine-treated patients.
Fl- aħħar tad- dożi, fost pazjenti li komplew it- trattament b’ entecavir għal aktar minn 52 ġimgħa (medja ta ’ 96 ġimgħa), 81% mill- 243 pazjent ttrattat b’ entecavir u 39% mill- 164 pazjent ttrattat b’ lamivudine kellhom DNA ta ’ HBV < 300 kopja/ ml skond il- PCR waqt li normalizzazzjoni fl- ALT (≤ 1 x ULN) seħħet f’ 79% tal- pazjenti ttrattati b’ entecavir u f’ 68% tal- pazjenti ttrattati b’ lamivudine.