qanastek/EMEA-V3 huggingface dataset:
There were no observed clinically significant adverse interactions in patients taking lamivudine concurrently with commonly used immunosuppressant medicinal products (e. g. cyclosporin A).
Ma ġewx osservati xi interazzjonijiet kliniċi sostanzjalment ħżiena f' pazjenti li kienu qed jieħdu lamivudine flimkien ma 'prodotti mediċinali immunosuppressant li jintużaw ħafna (eż. cyclosporin A).
However, formal interaction studies have not been performed.
Madankollu, studji formali fuq interazzjoniet għadhom ma sarux.
Lamivudine may inhibit the intracellular phosphorylation of zalcitabine when the two medicinal products are used concurrently.
Lamivudine jista 'jimpedixxi l- phosporylation intraċellulari ta ’ zalcitabine meta ż- żewġ prodotti mediċinali jittieħdu flimkien.
Zeffix is therefore not recommended to be used in combination with zalcitabine.
Għalhekk mhuwiex rakkomandat li Zeffix jittieħed flimkien ma ’ zalcitabine.
Pregnancy: there are no adequate data from the use of lamivudine in pregnant women.
Tqala: m’ hemmx tgħarif biżżejjed dwar l- użu ta ’ lamivudine waqt it- tqala.
The potential risk to humans is unknown.
Mhux magħruf ir- riskju potenzjali fuq in- nies.
Consistent with passive transmission of the substance across the placenta, lamivudine concentrations in infant serum at birth were similar to those in maternal and cord serum at delivery.
Waqt li huma konsistenti fit- trasmissjoni passiva tas- sustanza minn ġol- plaċenta, il- konċentrazzjonijiet ta 'lamivudine fis- serum ta' trabi tat- twelid kienu l- istess bħal dawk fis- serum tal- mara u l- kurdun waqt it- twelid.
Although animal reproductive studies are not always predictive of the human response, administration is not recommended during the first three months of pregnancy (see section 4.4).
Għalkemm studji dwar ir- riproduttivita 'fl- annimali mhux dejjem ifissru l- istess effetti fil- bniedem, din il- mediċina mhix rakkomandata fl- ewwel tlett xhur tat- tqala (ara sezzjoni 4. 4).
Lactation: following oral administration, lamivudine was excreted in breast milk at similar concentrations to those found in serum.
Treddigħ: wara li ttieħed mill- ħalq, lamivudine tneħħa mill- ħalib ġos- sider fl- istess konċentrazzjonijiet misjuba fis- serum.
It is therefore recommended that mothers taking lamivudine do not breast feed their infants.
Hu għalhekk rakkomandat li ommijiet fuq lamivudine ma jreddgħux lit- trabi tagħhom.
In clinical studies of patients with chronic hepatitis B, lamivudine was well tolerated.
Fi studji kliniċi ta 'pazjenti b' epatite B kronika, it- tolleranza ta ’ lamivudine kienet tajba.
The incidence of adverse events and laboratory abnormalities (with the exception of elevations of ALT and CPK, see below) were similar between placebo and lamivudine treated patients).
Il- każi ta 'effetti ħżiena u anormalitajiet ta' laboratorju (bl- eċċezzjoni ta 'żidiet ta' ALT u CPK, ara hawn taħt) kienu l- istess bħal bejn pazjenti li ħadu plaċebo u lamivudine.
The most common adverse events reported were malaise and fatigue, respiratory tract infections, throat and tonsil discomfort, headache, abdominal discomfort and pain, nausea, vomiting and diarrhoea.
L- iktar effetti ħżiena komuni rappurtati kienu telqa u għejja, infezzjonijiet fl- apparat respiratorju, uġigħ ħafif fil- gerżuma u t- tonsilli, uġigħ ta 'ras, uġigħat ta' żaqq, u uġigħ, nawsja, rimettar u dijareja.
Adverse reactions are listed below by system organ class and frequency.
5 Effetti aversi huma elenkati hawn taħt skond is- sistema, l- organu, il- klassi u l- frekwenza.
Frequency categories are only assigned to those adverse reactions considered to be at least possibly causally related to lamivudine.
Kategoriji ta 'frekwenza jingħataw biss għal dawk ir- reazzjonijiet ħżiena ikkunsidrati li jkunu għallinqas possibilment kaġunati minn lamivudine.
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1000) and very rare (< 1/ 10,000).
Il- frekwenzi huma definiti hekk: komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100, < 1/ 10), mhux komuni (≥ 1/ 1000, < 1/ 100), rari (≥ 1/ 10, 000, < 1/ 1000) u rari ħafna (< 1/ 10, 000).
5 The frequency categories assigned to the adverse reactions below are estimates: for most events, suitable data for calculating incidence are not available.
Il- kategoriji ta 'frekwenza marbutin ma' reazzjonijiet aversi kif jidhru hawn taħt huma bażati fuq stima: għall- biċċa l- kbira ta ’ l- eventi, m' hawnx it- tagħrif meħtieġ għall- kalkolu ta 'inċidenzi.
Very common and common adverse drug reaction frequency categories were determined from clinical trial data and the background incidence in placebo groups was not taken into account.
Kategoriji ta 'frekwenza komuni ħafna, u komuni, ta' reazzjoni aversi għall- mediċina ġew determinati minn tagħrif minn provi kliniċi, u l- inċidenza sekondarja fil- gruppi ta 'plaċebo ma ġietx ikkunsidrata.
Adverse drug reactions identified through post-marketing surveillance were categorised as rare or very rare.
Reazzjonijiet aversi magħrufa wara stħarriġ ta 'wara li l- prodott tpoġġa fuq is- suq ġew klassifikati bħala rari jew rari ħafna.
Thrombocytopenia
Thrombocytopenia.
Hepatobiliary disorders:
Disturbi fil- fwied u fil- marrara Komuni ħafna:
ALT elevations (see section 4.4).
Żieda ta 'ALT (ara sezzjoni 4. 4).
Exacerbations of hepatitis, primarily detected by serum ALT elevations, have been reported ‘ on- treatment’ and following lamivudine withdrawal.
Ġie rrappurtat attakk qawwi ta ’ l- epatite, li titfaċċa fil- bidu b' żieda tas- serum ALT, waqt it- trattament u wara li titwaqqaf lamivudine.
Most events have been self-limited, however fatalities have been observed very rarely (see section 4.4).
Il- biċċa l- kbira tal- każi kienu limitati fihom infushom, madankollu rarament ħafna ġew osservati xi fatalitajiet (ara sezzjoni 4. 4).
Elevations of CPK Muscle disorders, including myalgia, cramps and rhabdomyolysis
Żieda ta 'CPKE Disturbi fil- muskoli, inklużi myalgia, bugħawwieġ u rhabdolyolysis.
In patients with HIV infection, cases of pancreatitis and peripheral neuropathy (or paresthesia) have been reported.
F' pazjenti nfettati bl- HIV, każi ta 'infjammazzjoni tal- frixa u newropatija periferali (jew parestiżja) ġew rappurtati.
In patients with chronic hepatitis B there was no observed difference in incidence of these events between placebo and lamivudine treated patients.
F' pazjenti b’ epatite B kronika ma ġietx notata xi differenza fl- inċidenza ta 'dawn il - każi bejn pazjenti li ħadu plaċebo u dawk li ħadu lamivudine.
Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of combination nucleoside analogue therapy in patients with HIV.
Każi ta 'lactic acidosis, xi drabi fatali, normalment flimkien ma' hepatomegaly u hepatic seatosis ġew rappurtati f' każi ta 'terapija analoga ta' tagħqid nucleoside f' pazjenti bl- HIV.
There have been rare reports of lactic acidosis in patients receiving lamivudine for hepatitis B.
Kien hemm rapporti rari ta 'lactic acidosis f’ pazjenti li kienu qegħdin jirċievu lamivudine għall- kura ta ’ l- epatite B.
Administration of lamivudine at very high dose levels in acute animal studies did not result in any organ toxicity.
Studji ta 'każi akuti ta' dożi f' livelli qawwijin ħafna ta 'lamivudine fl- annimali ma rriżultawx f' xi avvelenament ta' xi organu.
Limited data are available on the consequences of ingestion of acute overdoses in humans.
Jeżisti xi tagħrif limitat dwar il- konsegwenzi akuti mit- teħid ta 'dożi eċċessivi mill- bniedem.
No fatalities occurred, and the patients recovered.
Ma kien hemm ebda fatalitajiet, u l- pazjenti fiequ.
No specific signs or symptoms have been identified following such overdose.
Ma rriżultaw ebda sinjali speċifiċi wara t- teħid ta 'dożi eċċessivi bħal dawn.
If overdose occurs the patient should be monitored and standard supportive treatment applied as required.
Fil- każ ta 'overdose il- pazjent għandu jiġi monitorjat, u jingħata trattament ta' sostenn kif meħtieġ.
Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, although this has not been studied.
Billi l- lamivudine jippermetti dijalisi, fit- trattament ta 'overdose tista' tintuża dijalisi kontinwa tad - demm, għalkemm dan għadu ma ġiex studjat.
J05A F05.
Grupp farmakoterapewtiku: nucleoside analogue, ATC Code: J05 F05
Lamivudine is an antiviral agent which is active against hepatitis B virus in all cell lines tested and in experimentally infected animals.
Lamivudine huwa aġent antivirali attiv kontra l- virus ta 'l- epatite B fil- linji kollha ta' ċelluli ttestjati u fl- annimali infettati b' esperiment.
Lamivudine is metabolised by both infected and uninfected cells to the triphosphate (TP) derivative which is the active form of the parent compound.
6 Lamivudine hu metabolizzat b 'ċelluli infettati jew mhux infettati lid- derivattiv trifosfat (TP) li huwa l - forma attiva tat- taħlita parentali.
The intracellular half life of the triphosphate in hepatocytes is 17-19 hours in vitro.
In- nofs ħajja intraċellulari tat- trifosfat fil- hepatocytes hi ta '17- 19 il siegħa in vitro.
Lamivudine-TP acts as a substrate for the HBV viral polymerase.
Lamivudine- TP jaħdem bħala substrat għall- polymerase virali tal- HBV.
The formation of further viral DNA is blocked by incorporation of lamivudine-TP into the chain and subsequent chain termination.
Il- formazzjoni ta 'aktar DNA virali tiġi mblukkata bid- dħul ta ’ lamiduvine- TP fil- katina u t- tmiem sussegwenti tal- katina.
6 Lamivudine-TP does not interfere with normal cellular deoxynucleotide metabolism.
Lamivudine- TP ma jfixkilx il- metaboliżmu deoxynucleotide ċellulari normali.
It is also only a weak inhibitor of mammalian DNA polymerases alpha and beta.
Hu wkoll inibitur verament dgħajjef tad- DNA polymerases mammiferi alfa u beta.
Furthermore, lamivudine-TP has little effect on mammalian cell DNA content.
Barra hekk, lamivudine għandu ftit effett fuq il- kontenut ta 'DNA f' ċelluli mammiferi.
In assays relating to potential substance effects on mitochondrial structure and DNA content and function, lamivudine lacked appreciable toxic effects.
Fl- analiżi ta 'l- effetti possibbli tas- sustanza fuq struttura mitochondrial u l- kontenut u l- funzjoni ta' DNA, lamivudine ma nstabx li kellu xi effetti serji ta 'tossiċita'.
It has a very low potential to decrease mitochondrial DNA content, is not permanently incorporated into mitochondrial DNA, and does not act as an inhibitor of mitochondrial DNA polymerase gamma.
Għandu potenzjal baxx ferm biex inaqqas il- kontenut ta 'DNA mitochondrial, ma jsirx parti permanenti ta ’ DNA mitochondrial, u ma jaħdimx bħala inibitur ta' mitochondrial DNA polymerase gamma.
Experience in patients with HBeAg positive CHB and compensated liver disease: in controlled studies, 1 year of lamivudine therapy significantly suppressed HBV DNA replication [34-57% of patients were below the assay detection limits (Abbott Genostics solution hybridization assay, LLOD < 1.6pg/ ml)}, normalised ALT level (40-72% of patients), induced HBeAg seroconversion (HBeAg loss and HBeAb detection with HBV DNA loss [by conventional assay], 16-18% of patients), improved histology (38-52% of patients had a ≥ 2 point decrease in the Knodell Histologic Activity Index [HAI]) and reduced progression of fibrosis (in 3-17% of patients) and progression to cirrhosis.
Esperjenza f’ pazjenti b’ CHB pożittiv għall- HbeAg u mard kumpensat tal- fwied: fi studji kontrollati, sena waħda ta 'terapija b ’ lamivudine żammet sostanzjalment ir- replikazzjoni ta' DNA tal- HBV {34 - 57% ta 'pazjenti kellhom livelli taħt il- limiti li jitkejlu fl- assay (soluzzjoni Abbott Genostics hybridization assay, LLOD < 1. 6pg/ ml)}, ġiebet għan- normal il- livell ta' ALT (40- 72% ta 'pazjenti), ikkaġunat serokonverżjoni tal- HbeAg (telf ta' DNA tal- HbeAg u skoperta ta 'HbeAb b’ telf ta ’ HBV DNA [b’ assay konvenzjonali], 16- 18% ta' pazjenti), tejjbet l- istoloġija (38- 52% ta 'pazjenti kellhom tnaqqis ta ’ ≥2 punti fil- Knodell Histologic Activity Index [HAI]) u naqqset l- avanz ta' fibrożi (f’ 3- 17% ta ’ pazjenti) u l- avanz għaċ- ċirrożi.
Continued lamivudine treatment for an additional 2 years in patients who had failed to achieve HBeAg seroconversion in the initial 1 year controlled studies resulted in further improvement in bridging fibrosis.
Meta t- trattament b’ lamivudine tkompla għal sentejn oħra f’ pazjenti li ma rnexxilhomx jiksbu serokonverżjoni tal- HbeAg fl- ewwel sena ta ’ l- istudji kontrollati, dan irriżulta f’ aktar titjib fil- bridging tal- fibrożi.
In patients with YMDD variant HBV, 41/ 82 (50%) patients had improvement in liver inflammation and 40/ 56 (71%) patients without YMDD variant HBV had improvement.
F’ pazjenti bil- varjant YMDD tal- HBV, 41/ 82 (50%) pazjent kellhom titjib fl - infjammazzjoni tal- fwied u 40/ 56 (71%) pazjent mingħajr il- varjant YMDD tal- HBV kellhom titjib.
Improvement in bridging fibrosis occurred in 19/ 30 (63%) patients without YMDD variant and 22/ 44 (50%) patients with the variant.
Kien hemm titjib fil- bridging tal- fibrożi f’ 19/ 30 (63%) pazjent mingħajr il- varjant YMDD u 22/ 44 (50%) pazjent bil- varjant.
Five percent (3/ 56) of patients without the YMDD variant and 13% (11/ 82) of patients with YMDD variant showed worsening in liver inflammation compared to pre-treatment.
F’ ħamsa fil- mija (3/ 56) ta ’ pazjenti mingħajr il- varjant YMDD u f’ 13% (11/ 82) ta ’ pazjenti bil- varjant YMDD l- infjammazjoni tal- fwied marret għall- agħar meta paragunata ma ’ kif kienet qabel it- trattament.
Progression to cirrhosis occurred in 4/ 68 (6%) patients with the YMDD variant, whereas no patients without the variant progressed to cirrhosis.
F’ 4/ 68 (6%) pazjent bil- varjant YMDD, kien hemm avanz għal ċirrożi, filwaqt li fl- ebda pazjent mingħajr il- varjant kien hemm avanz għaċ- ċirrożi.
In an extended treatment study in Asian patients (NUCB3018) the HBeAg seroconversion rate and ALT normalisation rate at the end of the 5 year treatment period was 48% (28/ 58) and 47% (15/ 32), respectively.
Fi studju ta 'trattament fit- tul, f’ pazjenti Asjatiċi (NUCB3018), ir- rata ta' serokonverżjoni tal- HbeAg u r- rata ta 'normalizzazzjoni ta' l- ALT fl- aħħar tal- perjodu ta 'ħames snin trattament kienet ta ’ 48% (28/ 58) u 47% (15/ 32) rispettivament.
HBeAg seroconversion was increased in patients with elevated ALT levels; 77% (20/ 26) of patients with pre-treatment ALT > 2 x ULN seroconverted.
77% (20/ 26) ta 'pazjenti bl' ALT ta ’ qabel it- trattament > 2x ULN kellhom serokonverżjoni.
At the end of 5 years, all patients had HBV DNA levels that were undetectable or lower than pre-treatment levels.
Fl- aħħar tal- ħames snin, il- pazjenti kollha kellhom livelli ta 'DNA tal- HBV li ma jitkejjlux jew li kienu aktar baxxi meta mqabbla ma' livelli ta 'qabel it- trattament.
Further results from the trial by YMDD variant status are summarised in Table 2.
Aktar riżultati mill- prova skond l- istatus tal- varjant YMDD huma miġbura f’ Tabella 2.
Efficacy results 5 years by YMDD status (Asian Study) NUCB3018
Riżultati ta ’ effikaċja 5 snin skond l- istatus ta ’ YMDD (Studju Asjatiku) NUCB3018
Subjects,% (no.)
Suġġetti,% (no.)
YMDD variant HBV status HBeAg seroconversion
Status tal- varjant YMDD tal - HBV Serokonverżjoni tal- HBeAg
Non-YMDD1
(15/ 40) 72
- All patients - Baseline ALT ≤ 1 x ULN2 - Baseline ALT > 2 x ULN
Il- pazjenti kollha
(15/ 40) 72 (1/ 11) 33 (9/ 15) 100
(9/ 15) 100
Undetectable HBV DNA
Undetectable HBV DNA
Baseline 3
Linja bażi 3
Week 260 4
Ġimgħa 260 4
negative
negattiv
positive< baseline positive> baseline
pożittiv < linja bażi pożittiv > linja bażi
ALT normalisation
ALT normalisation
- Baseline
- Linja bażi
33
67
above normal
fuq in- normal
Week 260
Ġimgħa 260
above normal > baseline
fuq in- normal > linja bażi
Patients designated as YMDD variant were those with ≥ 5% YMDD variant HBV at any annual time-point during the 5-year period.
Pazjenti meqjusa bħala varjant YMDD kienu dawk b ’ ≥5% varjant YMDD tal- HBV f’ kwalunkwe sena tul il- perjodu 1 ta ’ ħames snin.
Patients categorised as non-YMDD variant were those with > 95% wild-type HBV at all annual time-points during the 5-year study period
Pazjenti kategorizzati bħala mingħajr il- varjant YMDD kienu dawk b ’ > 95% HBV tat- tip selvaġġ f’ kull sena tul il- perjodu ta ’ ħames snin ta ’ l- istudju.
Upper limit of normal Abbott Genostics solution hybridisation assay (LLOD < 1.6 pg/ ml Chiron Quantiplex assay (LLOD 0.7 Meq/ ml)
Limitu ta ’ fuq tan- normal Soluzzjoni Abbott Genostics hybridisation assay (LLOD < 1. 6 pg/ ml Chiron Quantiplex assay (LLOD 0. 7 Meq/ ml)
Comparative data according to YMDD status were also available for histological assessment but only up to three years.
Data komparattiva skond l- istatus tal- YMDD kienu wkoll disponibbli għal assessjar istoloġiku imma sa tlett snin biss.
In patients with YMDD variant HBV, 18/ 39 (46%) had improvements in necroinflammatory activity and 9/ 39 (23%) had worsening.
F’ pazjenti bil- varjant YMDD tal- HBV, 18/ 39 (46%) kellhom titjib fl- attività nekro - infjammatorja u 9/ 39 (23%) marru għal- agħar.
In patients without the variant, 20/ 27 (74%) had improvements in necroinflammatory activity and 2/ 27 (7%) had worsening.
F’ pazjenti mingħajr il- varjant, 20/ 27 (74%) kellhom titjib fl- attività nekro- infjammatorja u 2/ 27 (7%) marru għal- agħar.
Following HBeAg seroconversion, serologic response and clinical remission are generally durable after stopping lamivudine.
Wara s- serokonverżjoni ta ’ HBeAg, ir- rispons seroloġiku u t- titfija klinika ġeneralment jibqgħu wara li twaqqaf l- lamivudine.
However, relapse following seroconversion can occur.
Madankollu, wieħed jista jirkadi wara li jkun hemm serokonverżjoni.
In a long-term follow-up study of patients who had previously seroconverted and discontinued lamivudine, late virological relapse occurred in 39% of the subjects.
F’ studju ta ’ tkomplija fit- tul ta ’ pazjenti li kellhom serokonverżjoni qabel u waqqfu l- lamivudine, 39% tas - suġġetti marru lura viroloġikament wara żmien twil.
Therefore, following HBeAg seroconversion, patients should be periodically monitored to determine that serologic and clinical responses are being maintained.
Għalhekk, wara s- serokonverżjoni ta ’ HBeAg, pazjenti għandhom jiġu monitorjati perjodikament biex wieħed ikun ċert li r- rispons seroloġiku u kliniku jibqa tajjeb.
In patients who do not maintain a sustained serological response, consideration should be given to retreatment with either lamivudine or an alternative antiviral agent for resumption of clinical control of HBV.
F’ pazjenti li ma jżommux rispons seroloġiku għal żmien twil, għandu jiġi kkunsidrat trattament mil- bidu b’ lamivudine jew sustanza antivirali alternattiva biex jerġa ’ jkun hemm kontroll kliniku tal- HBV.
In patients followed for up to 16 weeks after discontinuation of treatment at one year, post-treatment ALT elevations were observed more frequently in patients who had received lamivudine than in patients who had received placebo.
8 F' pazjenti li baqgħu jiġu segwiti sa 16- il ġimgħa wara l- waqfien tat- trattament fl- ewwel sena, żidiet fil- livelli ta 'l- ALT ta' wara t- trattament kienu osservati iktar ta 'spiss f' pazjenti li kienu ħadu l - lamivudine milli dawk tal- plaċebo.
A comparison of post-treatment ALT elevations between weeks 52 and 68 in patients who discontinued lamivudine at week 52 and patients in the same studies who
Paragun taż- żidiet fl- ALT ta ’ wara t- trattament bejn il- ġimgħa 52 u l- ġimgħa 68 f' pazjenti li ma baqgħux jieħdu l- lamivudine fil- ġimgħa 52 u pazjenti fl- istes studji li kienu ħadu plaċebo matul il- kors tat- trattament kollu jidher fit- Tabella 3.
The proportion of patients who had post-treatment ALT elevations in association with an increase in bilirubin levels was low and similar in patients receiving either lamivudine or placebo.
Kien hemm proporzjon baxx ta ’ pazjenti li kellhom żidiet fl- ALT wara t- trattament flimkien ma ’ żidiet fil- livelli ta ’ bilirubin u dan kien simili f’ pazjenti fuq lamivudine jew fuq plaċebo.
Post-treatment ALT Elevations in 2 Placebo-Controlled Studies in Adults
Żidiet fl- ALT ta 'Wara t- Trattament f' Żewġ Studji Kontrollati bil- Plaċebo f' Adulti
ALT ≥ 2 x baseline value ALT ≥ 3 x baseline value† ALT ≥ 2 x baseline value and absolute ALT
Pazjenti b' żidiet ta 'ALT / Pazjenti b' osservazzjonijiet * Valur Mhux Normali ALT ≥ 2 x valur linja bażi ALT ≥ 3 x valur linja bażi † ALT ≥ 2 x valur linja bażi u ALT assolut
37/ 137 (27%) 29/ 137 (21%)
Lamivudine 37/ 137 (27%) 29/ 137 (21%)
> 500 IU/ l ALT ≥ 2 x baseline value; and bilirubin > 2 x ULN
> 500 IU/ L ALT ≥2 x valur linja bażi; u bilirubin > 2 x ULN and
and ≥ 2 x baseline value *Each patient may be represented in one or more category. †
≥2 x valur linja bażi
1/ 137 (0.7%)
1/ 137 (0. 7%)
1/ 116 (0.9%)
1/ 116 (0. 9%)
ULN = Upper limit of normal.
* Kull pazjent jista 'jkun rappreżentat f' kategorija waħda jew iżjed. † Paragunabbli ma' tossiċita 'ta' Grad 3 skond kriterji modifikati tal- WHO ULN=Il- limitu ta 'fuq tan- normal.
Experience in patients with HBeAg negative CHB: initial data indicate the efficacy of lamivudine in patients with HBeAg negative CHB is similar to patients with HBeAg positive CHB, with 71% of patients having HBV DNA suppressed below the detection limit of the assay, 67% ALT normalisation and 38% with improvement in HAI after one year of treatment.
Esperjenza f’ pazjenti b’ CHB negattiv għall- HbeAg: l- ewwel tagħrif jindika li l- effikaċja ta ’ lamivudine f' pazjenti b’ CHB negattiv għall- HbeAg tixbah dik f’ pazjenti b’ CHB pożittiv għall- HbeAg, b’ 71% ta ’ pazjenti fejn tbaxxa l- HBV DNA għal taħt il- limitu ta ’ detection ta ’ l’ assay, 67% normalizzazzjoni ta ’ ALT u 38% b' titjib ta 'HAI wara sena ta ’ trattament..
When lamivudine was discontinued, the majority of patients (70%) had a return of viral replication.
Meta twaqqaf il - lamivudine, il- maġġoranza tal- pazjenti (70%) kellhom ritorn tar- replikazzjoni tal- virus.
Data is available from an extended treatment study in HBeAg negative patients (NUCAB3017) treated with lamivudine.
Hemm tagħrif minn studju ta ’ trattament fit- tul, f' pazjenti negattivi għall- HbeAg (NUCAB3017) li rċevew trattament b’ lamivudine.
After two years of treatment in this study, ALT normalisation and undetectable HBV DNA occurred in 30/ 69 (43%) and 32/ 68 (47%) patients respectively and improvement in necroinflammatory score in 18/ 49 (37%) patients.
Wara sentejn ta ’ trattament f’ dan l- istudju, kien hemm normalizzazzjoni ta ’ ALT u HBV DNA li ma jkunx osservat f’ 30/ 69 (43%) u 32/ 68 (47%) pazjent rispettivament u titjib fl- iskore nekro- infjammatorju f’ 18/ 49 (37%) pazjent.
In patients without YMDD variant HBV, 14/ 22 (64%) showed improvement in necroinflammatory score and 1/ 22 (5%) patients worsened compared to pre-treatment.
F’ pazjenti mingħajr il - varjant YMDD tal- HBV, 14/ 22 (64%) urew titjib fl- iskore nekro- infjammatorju u 1/ 22 (5%) pazjent mar għal- agħar meta mqabbel ma ’ qabel ma mbeda t- trattament.
In patients with the variant, 4/ 26 (15%) patients showed improvement in necroinflammatory score and 8/ 26 (31%) patients worsened compared to pre-treatment.
F’ pazjenti bil- varjant, 4/ 26 (15%) pazjenti wrew titjib fl- iskore nekro- infjammatorju u 8/ 26 (31%) pazjenti marru għal- agħar meta mqabbla ma ’ qabel ma mbeda t- trattament.
No patients in either group progressed to cirrhosis.
Ma kienx hemm pazjenti fl- ebda grupp li kellhom ċirrożi.
Frequency of emergence of YMDD variant HBV and impact on the treatment response: lamivudine monotherapy results in the selection of YMDD variant HBV in approximately 24% of patients following one year of therapy, increasing to 67% following 4 years of therapy.
Frekwenza tal- ħruġ tal- varjant YMDD tal- HBV u l- effett fuq ir- rispons tat- trattament: monoterapija bil- lamivudine twassal għas- selezzjoni tal- varjant YMDD tal- HBV f’ bejn wieħed u ieħor 24% ta ’ pazjenti wara sena ta ’ terapija u din tiżdied għal 67% wara erba snin ta ’ terapija.
Development of YMDD variant HBV is associated with reduced treatment response in some patients, as evidenced by increased HBV DNA levels and ALT elevations from previous on-therapy levels, progression of signs and symptoms of hepatitis disease and/ or worsening of hepatic necroinflammatory findings.
L- iżvilupp tal - varjant YMDD tal- HBV huwa assoċjat f’ xi pazjenti, ma ’ rispons mnaqqas għat- trattament, kif muri mil- livell ogħla ta ’ HBV DNA u ta ’ ALT meta mqabbel mal- livelli ta ’ waqt terapija ta ’ qabel, mis - sinjali u s- sintomi avvanzati tal- mard tal- fwied u/ jew is- sejbiet nekro- infjammatorji epatiċi li sejrin għall- agħar.
The optimal therapeutic management of patients with YMDD variant HBV has not yet been established (see section 4.4).
L- aħjar trattament għal- pazjenti bil- varjant YMDD tal- HBV għadu ma ġiex stabbilit (ara sezzjoni 4. 4).
In a double-blind study in CHB patients with YMDD variant HBV and compensated liver disease (NUC20904), with a reduced virological and biochemical response to lamivudine (n=95), the addition of adefovir dipivoxil 10 mg once daily to ongoing lamivudine 100mg for 52 weeks resulted in a median decrease in HBV DNA of 4.6 log10 copies/ ml compared to a median increase of 0.3 log10 copies/ ml in those patients receiving lamivudine monotherapy.
F’ studju double- blind f’ pazjenti b’ CHB bil- varjant YMDD tal- HBV u b’ mard kumpensat tal- fwied (NUC20904), b’ rispons viroloġiku u bijokimiku għal lamivudine mnaqqas (n=95), iż- żieda ta ’ adefovir dipivoxil 10 mg darba kuljum ma ’ terapija għaddeja ta ’ lamivudine 100mg għal 52 ġimgħa rriżulta f’ nuqqas medju fl- HBV DNA ta ’ 4. 6 log10 kopji/ ml meta komparat ma ’ żieda medja ta ’ 0. 3 log10 kopji/ ml f’ dawk il- pazjenti li kienu qed jirċievu lamivudine bħala monoterapija.
Normalisation of ALT levels occurred in 31% (14/ 45) of patients receiving combined therapy versus 6% (3/ 47) receiving lamivudine alone.
Il- livell ta ’ ALT ġie għan- normal f’ 31% (14/ 45) ta ’ pazjenti li kienu qed jirċievu terapija kumbinata meta komparat ma ’ 6% (3/ 47) li kienu qed jirċievu lamivudine waħdu.
Forty patients (HBeAg negative or HBeAg positive) with either decompensated liver disease or recurrent HBV following liver transplantation and YMDD variant were also enrolled into an open label arm of the study.
9 Erbgħajn pazjent (negattivi għal HBeAg jew pożittivi għal HBeAg) b’ mard mhux kumpensat tal- fwied jew b’ HBV li reġa ’ tfaċċa wara trapjant tal- fwied u bil- varjant YMDD daħlu wkoll f’ parti open label ta ’ l- istudju.
Addition of 10 mg adefovir dipivoxil once daily to ongoing lamivudine 100mg for 52 weeks resulted in a median decrease in HBV DNA of 4.6 log10 copies/ ml.
Żieda ta ’ 10 mg adefovir dipivoxil darba kuljum ma ’ terapija għaddeja ta ’ lamivudine 100mg għal 52 ġimgħa rriżulta f’ nuqqas medju fl- HBV DNA ta ’ 4. 6 log10 kopji/ ml.
Improvement in liver function was also seen after one year of therapy
Ntwera wkoll titjib fil- funzjoni tal- fwied wara sena ta ’ terapija.
9 Experience in patients with decompensated liver disease: placebo controlled studies have been regarded as inappropriate in patients with decompensated liver disease, and have not been undertaken.
Esperjenza f’ pazjenti b’ mard mhux kumpensat tal- fwied: studji kontrollati bi plaċebo ġew meqjusa mhux addattati għal pazjenti b' mard mhux kumpensat tal- fwied, u għalhekk ma sarux.
In non-controlled studies, where lamivudine was administered prior to and during transplantation, effective HBV DNA suppression and ALT normalisation was demonstrated.
Fi studji mhux kontrollati, meta lamivudine ingħata qabel u waqt trapjant, deher trażżin effettiv ta ’ HBV DNA u normalizzazzjoni ta 'ALT.
When lamivudine therapy was continued post transplantation there was reduced graft re-infection by HBV, increased HBsAg loss and on one-year survival rate of 76 – 100%.
Meta tkompliet il- kura b’ lamivudine wara trapjant kien hemm tnaqqis ta 're- infezzjoni tal- graft bl- HBV, żieda f' telf ta ’ HbsAg u fuq rata ta' sena ta 'sopravivenza ta ’ 76- 100%.
As anticipated due to the concomitant immunosuppression, the rate of emergence of YMDD variant HBV after 52 weeks treatment was higher (36% - 64%) in the liver transplant population than in the immunocompetent CHB patients (14% - 32%).
Kif kien maħsub minħabba l- immunosuppression konkomitanti, ir- rata tal- varjant YMDD tal- HBV li bdiet titfaċċa wara 52 ġimgħa ta 'trattament kienet akbar (36% - 64%) f' dawk bi trapjant tal- fwied milli f' pazjenti immunokompetenti b’ CHB (14% - 32%).
Experience in CHB patients with advanced fibrosis or cirrhosis: in a placebo-controlled study in 651 patients with clinically compensated chronic hepatitis B and histologically confirmed fibrosis or cirrhosis, lamivudine treatment (median duration 32 months) significantly reduced the rate of overall disease progression (34/ 436, 7.8% for lamivudine versus 38/ 215, 17.7% for placebo, p=0.001), demonstrated by a significant reduction in the proportion of patients having increased Child-Pugh scores (15/ 436, 3.4% versus 19/ 215, 8.8%, p=0.023) or developing hepatocellular carcinoma (17/ 436, 3.9% versus 16/ 215, 7.4%, p=0.047).
Esperjenza f’ pazjenti b’ CHB b’ fibrożi f’ stat avvanzat u b’ ċirożi: f’ studju kontrollat bi plaċebo f’ 651 pazjent bl- epatite B kronika kumpensata klinikament u b’ fibrożi jew ċirożi konfermati istoloġikament, trattament b’ lamivudine (tul ta ’ żmien medju 32 xahar) naqqas sinifikament ir- rata ta 'l- iżvilupp totali tal- marda (34/ 436, 7. 8% għal lamivudine kontra 38/ 215, 17. 7% għal plaċebo, p=0. 001), u dan intwera b’ tnaqqis sostanzjali fil- proporzjon ta ’ pazjenti b’ żieda fil- Child- Pugh scores (15/ 436, 3. 4% kontra 19/ 215, 8. 8%, p=0. 023) jew dawk li żviluppaw karċinoma epatoċellulari (17/ 436, 3. 9% kontra 16/ 215, 7. 4%, p=0. 047).
The rate of overall disease progression in the lamivudine group was higher for subjects with detectable YMDD variant HBV DNA (23/ 209, 11%) compared to those without detectable YMDD variant HBV (11/ 221, 5%).
Ir- rata ta ’ l- iżvilupp totali tal- marda fil- grupp tal- lamivudine kienet ogħla f’ dawk is- suġġetti bil- varjant YMDD tal- HBV DNA li jista jiġi osservat (23/ 209, 11%) meta mqabbla ma ’ dawk mingħajr il- varjant YMDD tal- HBV li jista jiġi osservat (11/ 221, 5%).
However, disease progression in YMDD subjects in the lamivudine group was lower than the disease progression in the placebo group (23/ 209, 11% versus 38/ 214, 18% respectively).
Madankollu, l - iżvilupp tal- marda f’ suġġetti b’ YMDD fil- grupp tal- lamivudine kien anqas mill- iżvilupp tal- marda fil - grupp plaċebo (23/ 209, 11% kontra 38/ 214, 18% rispettivament).
Confirmed HBeAg seroconversion occurred in 47% (118/ 252) of subjects treated with lamivudine and 93% (320/ 345) of subjects receiving lamivudine became HBV DNA negative (VERSANT [version 1], bDNA assay, LLOD < 0.7 MEq/ ml) during the study.
Serokonverżjoni ta ’ HBeAg konfermata seħħet f’ 47% (118/ 252) ta ’ suġġetti li rċevew trattament b’ lamivudine u 93% (320/ 345) ta ’ suġġetti li kienu qed jirċievu lamivudine saru negattivi għal HBV DNA (VERSANT [verżjoni 1], bDNA assay, LLOD < 0. 7 MEq/ ml) waqt l- istudju.
Experience in children and adolescents: lamivudine has been administered to children and adolescents with compensated CHB in a placebo controlled study of 286 patients aged 2 to 17 years.
Esperjenza fit- tfal u adolexxenti: lamivudine ingħata lil tfal u adolexxenti b' CHB kumpensat fi studju kontrollat bi plaċebo f' 286 pazjenti bejn is- sentejn u 17- il sena.
This population primarily consisted of children with minimal hepatitis B.
Din il- popolazzjoni kienet magħmula primarjament minn tfal b' epatite B minima.
A dose of 3 mg/ kg once daily (up to a maximum of 100 mg daily) was used in children aged 2 to 11 years and a dose of 100 mg once daily in adolescents aged 12 years and above.
Doża ta '3 mg/ kg kuljum (sa massimu ta' 100 mg kuljum) intużat fi tfal bejn is- sentejn u l- 11- il sena u doża ta '100 mg darba kuljum f' adolexxenti ta' minn 12- il sena 'l fuq.
This dose needs to be further substantiated.
Din id- doża trid tiġi sostanzjata aktar.
The difference in the HBeAg seroconversion rates (HBeAg and HBV DNA loss with HBeAb detection) between placebo and lamivudine was not statistically significant in this population (rates after one year were 13% (12/ 95) for placebo versus 22% (42/ 191) for lamivudine; p=0.057).
Id- differenza bejn ir- rati ta 'serokonverżjoni (telf ta' HBV DNA bi skoperta ta 'HbcAb) bejn plaċebo u lamivudine ma kienitx statistikament sinifikanti f' din il- popolazzjoni (ir- rati wara sena kienu 13% (12/ 95) għal plaċebo kontra 22% (42/ 191) għal lamivudine; p=0. 057).
The incidence of YMDD variant HBV was similar to that observed in adults, ranging from 19% at week 52 up to 45% in patients treated continuously for 24 months..
L- inċidenza tal- varjant YMDD tal- HBV kienet simili għal dik osservata fl - adulti u kienet tvarja bejn 19% (31/ 166) fil- ġimgħa 52 sa 45% (53/ 118) f' pazjenti li baqgħu kontinwament fuq it- trattament għal 24 xahar.
Lamivudine is well absorbed from the gastrointestinal tract, and the bioavailability of oral lamivudine in adults is normally between 80 and 85%.
Lamivudine hu assorbit sew mill- parti gastro- intestinali, u l- biodisponibilita 'ta' lamivudine li jittieħed mill- ħalq minn adulti hi normalment bejn 80% u 85%.
100 mg once daily, Cmax is in the order of 1.1-1.5 µg/ ml and trough levels were 0.015-0.020 µg/ ml.
Wara li din il- mediċina tkun ittieħdet mill- ħalq, il- ħin medju (tmax) għal konċentrazzjonijiet massimi ta 'serum hu bejn wieħed u ieħor ta' 1. 1- 1. 5 µg/ ml u l- livelli t' isfel kienu 0. 015- 0. 020 µg/ ml.
Co-administration of lamivudine with food resulted in a delay of tmax and a lower Cmax (decreased by up to 47%).
It- teħid ta 'lamivudine ma' l- ikel irriżulta f' dewmien ta 'tmax u ta' Cmax aktar baxx (tnaqqas sa 47%).
However, the extent (based on the AUC) of lamivudine absorbed was not influenced, therefore lamivudine can be administered with or without food.
Madankollu, il- miżura (bażata fuq l- AUC) ta 'lamivudine assorbit ma ġietx influwenzata, għalhekk lamivudine jista' jittieħed ma 'l- ikel jew mhux ma' l- ikel.
From intravenous studies the mean volume of distribution is 1.3 l/ kg.
Studji ta 'ġol- vini juru li l- volum medju ta' distribuzzjoni hu 1. 3 l/ kg.
Lamivudine exhibits linear pharmacokinetics over the therapeutic dose range and displays low plasma protein binding to albumin.
Lamivudine juri farmakokinetiċi lineari fuq il- medda ta 'dożi terapewtiċi u juri rabta baxxa ta' proteina tal- plażma għall- albumina.
10 Metabolism:
10 Tagħrif limitat juri li lamivudine jidħol fis- sistema ċentrali nervuża u jilħaq il- fluwidu ċerebro- spinali (CSF).
Lamivudine is predominately cleared by renal excretion of unchanged substance.
Lamivudine jitneħħa prinċipalment permezz ta 'tnixxija mill- kliewi ta' sustanza mhux mibdula.
The likelihood of metabolic substance interactions with lamivudine is low due to the small (5-10%) extent of hepatic metabolism and the low plasma protein binding.
Ftit hemm probabilta 'ta' azzjoni metabolika reċiproka mal- lamivudine minħabba l - okkorrenza baxxa (5- 10%) ta 'metaboliżmu tal- fwied u t- taghħqid tal- proteina fil- plażma baxx.
The mean systemic clearance of lamivudine is approximately 0.3 l/ h/ kg.
It- tneħħija medja mis- sistema ta ’ lamivudine hi bejn wieħed u ieħor ta '0. 3 l/ h/ kg.
The observed half-life of elimination is 5 to 7 hours.
In- nofs ħajja tat- tneħħija osservata hi minn 7 sa 6 siegħat.
The majority of lamivudine is excreted unchanged in the urine via glomerular filtration and active secretion (organic cationic transport system).
Il- biċċa l' kbira ta ’ lamivudine titneħħa bla tinbidel fl- awrina b’ filtrazzjoni glomerulari u bi tneħħija attiva (is- sistema ta trasport katjoniku organika).
Renal clearance accounts for about 70% of lamivudine elimination.
It - tneħħija ta 70% ta ’ lamivudine issir mill- kliewi.
Special populations:
Popolazzjonijiet Speċjali:
Studies in patients with renal impairment show lamivudine elimination is affected by renal dysfunction.
Studji fuq pazjenti b' mard fil- kliewi juru li t- tneħħija ta ’ lamivudine hi affettwata minn kliewi li ma jiffunzjonawx tajjeb.
Dose reduction in patients with a creatinine clearance of < 50 ml/ min is necessary (see section 4.2).
Tnaqqis tad- doża hu meħtieġ f' pazjenti bi tneħħija ta 'kreatinina ta ’ < 50 ml/ min (ara sezzjoni 4. 2)
The pharmacokinetics of lamivudine are unaffected by hepatic impairment.
Il- farmakokinetiċi ta ’ lamivudine ma jintlaqtux ħażin mill- mard tal- fwied.
Limited data in patients undergoing liver transplantation, show that impairment of hepatic function does not impact significantly on the pharmacokinetics of lamivudine unless accompanied by renal dysfunction.
Tagħrif limitat minn pazjenti li jkunu qed jagħmlu trapjant tal- fwied juri li mard tal- fwied ma tantx għandu effett fuq il - farmakokinetika ta ’ lamivudine sakemm ma jkunx hemm ukoll mard tal- kliewi.
In elderly patients the pharmacokinetic profile of lamivudine suggests that normal ageing with accompanying renal decline has no clinically significant effect on lamivudine exposure, except in patients with creatinine clearance of < 50 ml/ min (see section 4.2).
F' pazjenti anzjani il- profil farmakokinetiku ta ’ lamivudine jindika li l- avanz fl- eta 'bin- nuqqas li jġib fil- funzjonament tal- kliewi m' għandux xi effett partikolari fuq l- esponiment ta ’ lamivudine, ħlief f' pazjenti bi tneħħija ta' kreatinina ta < 50 ml/ min (ara sezzjoni 4. 2).
Administration of lamivudine in animal toxicity studies at high doses was not associated with any major organ toxicity.
It- teħid ta 'lamivudine f' dożi kbar fi studji dwar tossiċita' fl- annimali ma wera ebda tossiċita 'serja ta' xi organi.
At the highest dosage levels, minor effects on indicators of liver and kidney function were seen together with occasional reduction in liver weights.
Fl- ogħla livelli ta 'dożaġġ, dehru xi effetti żgħar fuq indikaturi tal- funzjonament tal- fwied u l - kliewi flimkien ma' xi tnaqqis fil- piżijiet tal- fwied.
Reduction of erythrocytes and neutrophil counts were identified as the effects most likely to be of clinical relevance.
It- tnaqqis ta 'eritroċiti u ta' newtrofili ġew identifikati bħala l- effetti l- iktar probabbli ta 'relevanza klinika.
These events were seen infrequently in clinical studies.
Dawn il- każi rarament dehru fi studji kliniċi.
Lamivudine was not mutagenic in bacterial tests but, like many nucleoside analogues showed activity in an in vitro cytogenetic assay and the mouse lymphoma assay.
Lamivudine ma kienx mutaġeniku f' testijiet ta 'batterji, biss bħal ħafna analogi nucleosidi wera attivita' f' analiżi ċitoġenetika in vitro u f' analiżi ta 'limfoma fil- ġurdien.
Lamivudine was not genotoxic in vivo at doses that gave plasma concentrations around 60-70 times higher than the anticipated clinical plasma levels.
Lamivudine ma kienx ġenotossiku in vivo f' dożi li rriżultaw f' konċentrazzjonijiet ta 'plażma 60- 70 darba iktar mill- livelli ta' plażma klinika antiċipati.
As the in vitro mutagenic activity of lamivudine could not be confirmed by in vivo tests, it is concluded that lamivudine should not represent a genotoxic hazard to patients undergoing treatment.
Billi l- attivita 'mutaġenika ta ’ lamivudine ma setgħetx tiġi konfermata b' testijiet in vitro, jista' jiġi konkluż li lamivudine m' għandux ikun ta 'riskju ġenotossiku għal pazjenti li jkunu qed jieħduh.
Reproductive studies in animals have not shown evidence of teratogenicity and showed no effect on male or female fertility.
Studji dwar ir- riproduzzjoni fl- annimali ma wrewx evidenza ta ’ effett teratoġeniku u ma wrew l- ebda effett fuq il- fertilità tar- raġel jew tal- mara.
Lamivudine induces early embryolethality when administered to pregnant rabbits at exposure levels comparable to those achieved in man, but not in the rat even at very high systemic exposures.
Lamivudine għandu effett letali kmieni fl- iżvilupp ta ’ l - embriju meta ngħata lil fniek waqt it- tqala meta dawn ġew esposti għal livell komparabbli ma ’ dak fil - bniedem, imma ma kellux dan l- effett fil- far anke meta dan ġie espost għal livell fid- demm ogħli ħafna.
The results of long term carcinogenicity studies with lamivudine in rats and mice did not shown any carcinogenic potential.
Ir- riżultati ta 'studji karċinoġeniċi fit- tul ta ’ lamivudine fi ġrieden kbar u żgħar ma wrewx potenzjal karċinoġeniku.
11 6.
11
Microcrystalline Cellulose Sodium Starch Glycollate Magnesium Stearate
Sodium Starch Glycolate Magnesium Stearate
Hypromellose Titanium Dioxide Macrogol 400 Polysorbate 80 Synthetic yellow and red iron oxides
Titanium Dioxide Macrogol 400 Polysorbate 80 Iron oxides, sintetiċi, sofor u ħomor
Do not store above 30ºC.
Taħżinx f' temperatura 'l fuq minn 30oC
Boxes containing 28 or 84 film-coated tablets in double foil blisters, laminated with polyvinyl chloride.
Kaxxi li fihom 28 jew 84 pilloli miksija ġo double foil blisters, laminati bi klorur tal- polyvinyl
Any unused product should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża għandu jintrema kif jitolbu l- liġijiet lokali
29 July 1999 Date of renewal of authorisation:
29 ta 'Lulju 1999 Data ta ’ tiġdid ta ’ l- awtorizzazzjoni:
Zeffix 5 mg/ ml oral solution
Soluzzjoni ta '5 mg/ ml ta' Zeffix li tittieħed mill- ħalq
Zeffix oral solution contains 5 mg/ ml lamivudine
Is- soluzzjoni Zeffix li tittieħed mill- ħalq fiha 5 mg/ ml lamivudine
Sugar (sucrose) and preservatives: methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216)
Zokkor (sucrose) u preservattivi: methyl parahydroxybenzoate (E218) u propyl parahydroxybenzoate (E216)
For a full list of excipients see section 6.1.
Għal lista sħiħa ta’ sustanzi mhux attivi ara sezzjoni 6. 1.
Clear, colourless to pale yellow in colour.
Ċar, bla kulur għal lewn isfar ċar.
Adults: the recommended dosage of Zeffix is 100 mg once daily.
Adulti: d- doża rakkomandata ta 'Zeffix hi ta' 100 mg darba kuljum.
• In patients with HBeAg positive chronic hepatitis B (CHB) treatment should be administered for at least 3-6 months after HBeAg seroconversion (HBeAg and HBV DNA loss with HBeAb detection) is confirmed, to limit the risk of virological relapse, or until HBsAg seroconversion.
• F' pazjenti bl- epatite B kronika (CHB) pożittiva għall- HbeAg it- trattament għandu jiġi amministrat għallinqas għal 3- 6 xhur wara li tiġi kkonfermata s- serokonverżjoni ta 'l- HbeAg (telf ta' HbeAg u HBV DNA bi skoperta ta 'HbeAB) biex jitnaqqas ir- riskju li l- pazjent jirkadi viroloġikament jew sas- serokonverżjoni tal- HbsAg.
Treatment discontinuation may be considered following HBsAg seroconversion. • In patients with either HBeAg positive or HBeAg negative CHB the development of YMDD variant HBV may result in a diminished therapeutic response to lamivudine, indicated by a rise in HBV DNA and ALT from previous on-treatment levels.
Waqfien tat- trattament jista 'jiġi kkunsidrat wara s- serokonverżjoni tal - HbsAg. • F' pazjenti b’ CHB pożittiva għall- HbeAg jew negattiva għall- HbeAg, l- iżvilupp tal- varjant YMDD ta ’ l- HBV jista jirriżulta f’ rispons terapewtiku mnaqqas għal lamivudine, li jintwera b’ żieda ta ’ l- HBV DNA u ta ’ l- ALT mill- livelli preċedenti ta ’ waqt it- trattament.
In patients with extended-duration
F’ pazjenti bil -
14 YMDD variant HBV, a switch to or addition of an alternative agent should be considered (see section 5.1). • In patients with decompensated liver disease and liver transplant recipients, treatment cessation is not recommended.
13 varjant YMDD ta ’ l- HBV li jdum għal żmien twil, l- użu ta ’ trattament alternattiv għandu jiġi kkunsidrat flimkien jew minnflok dan it- trattament (ara sezzjoni 5. 1). • F' pazjenti b' mard mhux kumpensat tal- fwied, u f’ dawk li għaddew minn trapjant tal- fwied il - waqfien tat- trattament mhux rakkomandat.
If Zeffix is discontinued, patients should be periodically monitored for evidence of recurrent hepatitis (see section 4.4).
(ara sezzjoni 4. 4).
Creatinine clearance ml/ min
Tneħħija ta 'kreatinina ml/ min
First Dose of Zeffix oral solution
L- ewwel doża ta 'taħlita likwida Zeffix li tittieħed mill- ħalq *
Maintenance Dose Once daily
Doża ta ’ manteniment Darba kuljum
30 to < 50
30 to < 50
Data available in patients undergoing intermittent haemodialysis (for less than or equal to 4 hrs dialysis 2-3 times weekly), indicate that following the initial dosage reduction of lamivudine to correct for the patient’ s creatinine clearance, no further dosage adjustments are required while undergoing dialysis.
It- tagħrif disponibbli dwar pazjenti għaddejjin minn proċess intermittenti ta 'dijaliżi tad- demm (ta' inqas minn, jew ugwali għal 4 sigħat dijaliżi 2- 3 darbiet kull ġimg] a), jindikaw li wara t- tnaqqis inizjali tad- dożaġġ ta 'lamivudine biex jagħmel tajjeb għat- tneħħija tal- kreatinina mill- pazjent, ma jibqax aktar ħtieġa għal aġġustamenti tad- dożaġġ waqt li jkun għaddej il- proċess ta' dijaliżi.
Hepatic impairment: data obtained in patients with hepatic impairment, including those with end-stage liver disease awaiting transplant, show that lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction.
Indeboliment fil- fwied: tagħrif miksub minn pazjenti b' indeboliment epatiku, inklużi dawk fl- aħħar fażi tal- mard fil- fwied li qed jistennew trapjant, juri li l- farmakokinetiċi tal- lamivudine mhumiex affettwati b' mod sinifikanti ta 'anormalita' ta 'funzjoni epatika.
Hypersensitivity to the active substance or to any of the excipients.
Sensittività ’ eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
15 Data are limited on the use of lamivudine in HBeAg negative (pre-core mutant) patients and in those receiving concurrent immunosuppressive regimes, including cancer chemotherapy.
14 Tagħrif dwar l- użu ta ’ lamivudine f' pazjenti b' HbeAg negattiv (mutant pre- core) u f' dawk li qed jirċievu concurrent immunosuppressive regimes, inkluża l- kemjoterapija għall- kanċer huwa limitat.
Exacerbations of hepatitis
Attakk qawwi ta ’ l- epatite
Exacerbation of hepatitis has primarily been detected by serum ALT elevations, in addition to the re-emergence of HBV DNA.
Il- peġġjorament ta 'l - epatite gie nnotat primarjament b' żieda tas- serum ALT, barra milli terġa' titfaċċa l- HBV DNA.
See Table 3 in Section 5.1 Clinical experience for more information regarding frequency of post treatment ALT elevations.
Esperjenza klinika għal aktar tagħrif dwar il- frekwenza ta 'żidiet ta' ALT wara t- trattament.
Most events have been self- limited, however some fatalities have been observed.
L- biċċa l- kbira tal- każi kienu limitati fihom infushom, madankollu ġew osservati xi fatalitajiet.
For patients who develop evidence of recurrent hepatitis post-treatment, there are insufficient data on the benefits of re-initiation of lamivudine treatment.
Għal pazjenti li jiżviluppaw sinjali ta 'epatite rikorrenti wara t- trattament, m' hemmx tagħrif biżżejjed dwar il- benefiċċji tat- trattament mill- ġdid b‘ lamivudine.
Due to the marginal liver function in these patients, hepatitis reactivation at discontinuation of lamivudine or loss of efficacy during treatment may induce severe and even fatal decompensation.
Billi f' dawn il- pazjenti l- fwied jaħdem ftit wisq, il- ħruġ mill- ġdid ta 'l- epatite mat - twaqqif tal- lamivudine jew in- nuqqas ta' effettivita 'waqt il- kura jistgħu iwasslu għal decompensation qawwija jekk mhux fatali.
HBV antigen/ antibody, and serum HBV DNA concentrations when possible.
Il- parametri tal- laboratorju li għandhom jiġu monitorjati għandhom jinkludu (mill- inqas) is- serum ALT, bilirubin, albumin, nitroġenu ta 'l- urea fid- demm, kreatinin, u status viroloġiku: konċentrazzjonijiet ta antiġenu/ anti- korp ta' l- HBV u ta 'serum HBV DNA meta possibbli.
For HIV co-infected patients not requiring anti-retroviral therapy, there is a risk of HIV mutation when using lamivudine alone for treating chronic hepatitis B.
Għal pazjenti ko- infettati bl- HIV mingħajr il- bżonn ta 'terapija anti- retroviral, hemm riskju ta' tibdil ta 'l- HIV meta jintuża lamivudine waħdu għall- kura ta' l- epatite B kronika.