natgillin/translations-raw huggingface dataset:
I de kliniske forsøg blev behandling med entecavir seponeret, hvis patienterne oplevede et præspecificeret respons.
In the clinical trials entecavir treatment was discontinued if patients achieved a prespecified response.
Immunsystemet: sjælden
Immune system disorders: rare
d ≥ 1 log10 stigning over nadir i HBV-DNA ved PCR, bekræftet ved på hinanden følgende målinger eller ved afslutningen af tidsvinduet.
d ≥ 1 log10 increase above nadir in HBV DNA by PCR, confirmed with successive measurements or at the end of the windowed time point.
Det observerede lægemiddelakkumuleringsindeks er ≈ 2 timer ved dosering én gang dagligt, hvilket tyder på en effektiv akkumuleringshalveringstid på ca. 24 timer.
The observed drug accumulation index is ≈ 2 times with once daily dosing, suggesting an effective accumulation half-life of about 24 hours.
Alle 61 patienter var HBsAg-negative efter transplantationen, og 2 af patienterne blev senere HBsAg-positive på trods af ikke-detekterbart HBV-DNA (<6 IE/ml).
All 61 patients had HBsAg loss post-transplantation, and 2 of these later became HBsAg positive despite maintaining undetectable HBV DNA (<6 IU/ml).
Entecavir var clastogent over for humane lymfocytkulturer ved koncentrationer, der var betragteligt større end de kliniske.
Entecavir was clastogenic to human lymphocyte cultures at concentrations substantially higher than those achieved clinically.
Du bør ikke tage Entecavir Accord for at behandle din hepatitis-B-infektion, medmindre du samtidig også tager medicin mod hiv, idet virkningen af fremtidig hivbehandling kan blive nedsat.
You should not take Entecavir Accord to treat your hepatitis B infection unless you are taking medicines for HIV at the same time, as the effectiveness of future HIV treatment may be reduced.
Behandlingen skal initieres af en læge med erfaring i behandling af kronisk hepatitis B-infektion.
Therapy should be initiated by a physician experienced in the management of chronic hepatitis B infection.
du skal ikke holde op med at tage Entecavir Accord uden at have talt med din læge om det først, da din hepatitis kan forværres, efter at behandlingen stoppes.
do not stop taking Entecavir Accord without your doctor's advice since your hepatitis may worsen after stopping treatment.
Hyppigheden og typen af bivirkninger i dette studie var sammenlignelige med de bivirkninger, der forventes hos patienter, som har gennemgået en levertransplantation, og i overensstemmelse med entecavirs kendte sikkerhedsprofil.
The frequency and nature of adverse events in this study were consistent with those expected in patients who have received a liver transplant and the known safety profile of entecavir.
Entecavir-TP er en svag hæmmer af cellulær DNA-polymerase α, β og δ med Ki værdier på 18 - 40 µM.
Entecavir-TP is a weak inhibitor of cellular DNA polymerases α, β, and δ with Ki values of 18 to 40 µM.
Opståen af entecavir genotype-resistens til og med År 5, lamivudin-refraktære forsøg År 1 År 2 År 3a
Genotypic Entecavir Resistance Through Year 5, Lamivudine-Refractory Studies Year 1 Year 2 Year 3a
Patienter, der vejer fra 10 kg til 32,5 kg, anbefales oral entecaviropløsning.
For patients weighing from 10 kg to 32.5 kg, an entecavir oral solution is recommended.
Entecavir var superior til adefovirdipivoxil mht. det primære endepunktgennemsnitlig ændring fra baseline i serum-HBV-DNA ved PCR i uge 24.
Entecavir was superior to adefovir dipivoxil on the primary efficacy endpoint of mean change from baseline in serum HBV DNA by PCR at week 24.
Hvis behandling seponeres uafhængigt af behandlingsrespons, kan forekomst af ALAT-stigninger efter seponering være højere.
If treatment is discontinued without regard to treatment response, the rate of post-treatment ALT flares could be higher.
Pædiatriske patienter med en kropsvægt på mindst 32,6 kg skal have en daglig dosis på en 0,5 mg tablet med eller uden mad.
Paediatric patients with a body weight of at least 32.6 kg, should be administered a daily dose of one 0.5 mg tablet with or without food.
Farmakoterapeutisk klassifikation: antivirale midler til systemisk brug, nukleosid og nukleotid revers transkriptase-hæmmere
Pharmacotherapeutic group: antivirals for systemic use, nucleoside and nucleotide reverse transcriptase inhibitors
SerumALAT og HBV-DNA-niveauer bør følges regelmæssigt efter seponering af behandlingen (se pkt.
Serum ALT and HBV DNA levels should be followed regularly after treatment discontinuation (see section 4.4).
Dertil kommer, at høj eksponering af entecavir ikke havde relevante bivirkninger på γ-polymerase eller mitochondriel DNA-syntese i HepG2-celler (Ki > 160 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).
Det vides ikke, om det er sikkert at bruge Entecavir Accord under graviditet.
It has not been demonstrated that Entecavir Accord is safe to use during pregnancy.
Entecavir Accord bør ikke anvendes til børn under 2 år eller børn, der vejer under 10 kg.
Entecavir Accord should not be used for children below 2 years of age or weighing less than 10 kg.
Disse forsøg tilvejebringer erfaring fra 195 nukleosid-naive, HBeAgpositive forsøgspersoner, som behandles med entecavir i gennemsnitlig 99 uger.
These trials provide experience in 195 HBeAg-positive nucleosidetreatment-naïve subjects treated with entecavir for a median duration of 99 weeks.
I et separat studie, hvor entecavir blev administreret til drægtige, diegivende rotter med 10 mg/kg, påvistes både føtal optagelse af entecavir og udskillelse af entecavir i mælken.
In a separate study wherein entecavir was administered to pregnant lactating rats at 10 mg/kg, both foetal exposure to entecavir and secretion of entecavir into milk were demonstrated.
Der bør udvises forsigtighed, når nukleosidanaloger ordineres til patienter (særligt overvægtige kvinder) med hepatomegali, hepatitis eller andre kendte risikofaktorer for leversygdom.
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.
I HBV-kombinationsassays i cellekulturer var abacavir, didanosin, lamivudin, stavudin, tenofovir og zidovudin ikke antagonistiske over for entecavirs anti-HBV-aktivitet inden for et større koncentrationsspænd.
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.
MINDSTEKRAV TIL MÆRKNING PÅ BLISTERKORT ELLER BLISTERSTRIPS BLISTERKORT/ALU-ALU BLISTERSTRIPS
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTERS/ALU-ALU BLISTER
Amning bør afbrydes under behandling med Entecavir Accord.
Breast-feeding should be discontinued during treatment with Entecavir Accord.
e Gennemsnitlig MELD-score ved baseline var 17,1 for ETV og 15,3 for adefovirdipivoxil.
e Baseline mean MELD score was 17.1 for ETV and 15.3 for adefovir dipivoxil.
Eliminering: Entecavir elimineres primært via nyrerne, hvor omkring 75% af dosis ved steady-state kan genfindes som uomdannet lægemiddel i urinen.
Elimination: entecavir is predominantly eliminated by the kidney with urinary recovery of unchanged drug at steady-state of about 75% of the dose.
Forsøgspersonerne blev randomiseret (2:1) til blindet behandling med entecavir 0,015 mg/kg op til 0,5 mg/dag (N = 120) eller placebo (N = 60).
Subjects were randomized (2:1) to receive blinded treatment with entecavir 0.015 mg/kg up to 0.5 mg/day (N = 120) or placebo (N = 60).
Dette fund blev ikke observeret i studier med gentagne doser til andre arter, inklusiv aber, der fik entecavir dagligt i 1 år i doser ≥ 100 gange den humane dosis.
This finding was not observed in repeat-dose studies in other species, including monkeys administered entecavir daily for 1 year at exposures ≥ 100 times those in humans.
Baseline HBVDNA < 8 log10 IE/ml Baseline HBV-DNA ≥ 8 log10 IE/ml aNC=F (noncompleter=svigt) * Patienter randomiseret til placebo, som ikke opnåede HBe-serokonvertering ved uge 48, skiftede til åben entecavir i studiets andet år; derfor foreligger der kun randomiserede sammenligningsdata indtil uge 48.
Baseline HBV DNA < 8 log10 IU/ml Baseline HBV DNA ≥ 8 log10 IU/ml aNC=F (noncompleter=failure) * Patients randomized to placebo who did not have HBe- seroconversion by Week 48 rolled over to open-label entecavir for the second year of the study; therefore randomized comparison data are available only through Week 48.
Bivirkninger, der som minimum vurderedes som muligvis at være forbundet med entecavir, angives efter organklasse nedenfor.
Adverse reactions considered at least possibly related to treatment with entecavir are listed by body system organ class.
Der er begrænsede data vedrørende patienter med samtidig hiv-infektion, som har lave CD4-tal (< 200 celler/mm3).
There are limited data on patients co-infected with HIV who have low CD4 cell counts (< 200 cells/mm3).
Hvis lægen har sagt, at du skal tage Entecavir Accord på tom mave, betyder det mindst 2 timer efter et måltid og mindst 2 timer før næste måltid.
If your doctor instructs you to take Entecavir Accord on an empty stomach, empty stomach means at least 2 hours after a meal and at least 2 hours before your next meal.
Lad derfor være med at give Entecavir Accord til andre.
Do not pass it on to others.
Patienter med fremskreden leversygdom eller cirrose kan have højere risiko for hepatisk inkompensation efter hepatitis-eksacerbation og bør derfor monitoreres tæt under behandling.
Patients with advanced liver disease or cirrhosis may be at a higher risk for hepatic decompensation following hepatitis exacerbation, and therefore should be monitored closely during therapy.
Lamivudin-refraktære patienter:
Lamivudine-refractory:
Patienter der responderede blev fulgt i yderligere 24 uger efter seponering af behandling.
Patients in response were followed for an additional 24 weeks offtreatment.
Blandt patienter med baseline Ishak fibrose-score ≥ 2, havde 25/43 (58%) ≥ 2 point fald.
For patients with baseline Ishak fibrosis score ≥ 2, 25/43 (58%)
Hvis oral opløsning ikke er tilgængelig, kan dosis alternativt justeres ved at øge dosisintervallet, som vist i tabellen.
As an alternative, in case the oral solution is not available, the dose can be adjusted by increasing the dosage interval, also shown in the table.
Behandling med nukleosidanaloger skal seponeres i tilfælde af hurtigt stigende aminotransferaseniveauer, progressiv hepatomegali eller metabolisk acidose/laktacidose af ukendt ætiologi.
Treatment with nucleoside analogues should be discontinued when rapidly elevating aminotransferase levels, progressive hepatomegaly or metabolic/lactic acidosis of unknown aetiology occur.
Gennemsnitlig EC50-værdi for entecavir mod LVDr HBV (rtL180M og rtM204V) er 0,026 µM (0,010 - 0,059 µM).
The median EC50 value for entecavir against LVDr HBV (rtL180M and rtM204V) was 0.026 µM (range 0.010-0.059 µM).
Administration af 0,5 mg entecavir med et fedtrigt standardmåltid (945 kcal, 54,6 g fedt) eller et let måltid (379 kcal, 8,2 g fedt) forårsagede en minimal forsinkelse i absorption (1 - 1,5 time efter fødeindtagelse vs. 0,75 time fastende), et fald i Cmax på 44 - 46% samt et fald i AUC på 18 - 20%.
Administration of 0.5 mg entecavir with a standard high-fat meal (945 kcal, 54.6 g fat) or a light meal (379 kcal, 8.2 g fat) resulted in a minimal delay in absorption (1-1.5 hour fed vs. 0.75 hour fasted), a decrease in Cmax of 44-46%, and a decrease in AUC of 18-20%.
Resistens medieres ved nedsat hæmmerbinding til den ændrede HBV-reverstranskriptase, og resistent HBV udviser nedsat replikationskapacitet i cellekulturer.
Resistance is mediated by reduced inhibitor binding to the altered HBV reverse transcriptase, and resistant HBV exhibits reduced replication capacity in cell culture.
Derudover kan patienter med inkompenseret leversygdom have større risiko for laktacidose og for specifikke renale bivirkninger, såsom hepatorenalt syndrom.
Also, patients with decompensated liver disease may be at higher risk for lactic acidosis and for specific renal adverse events such as hepatorenal syndrome.
Antiviral aktivitet: Entecavir hæmmer HBV-DNA-syntese (50% reduktion, EC50) ved en koncentration på 0,004 µM i humane HepG2-celler transficeret med vild-type HBV.
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.
For både kompenseret og inkompenseret leversygdom er denne indikation baseret på data fra kliniske forsøg hos nukleosid-naive patienter med HBeAg-positiv og HBeAg-negativ HBV-infektion.
For both compensated and decompensated liver disease, this indication is based on clinical trial data in nucleoside naive patients with HBeAg positive and HBeAg negative HBV infection.
Det anbefales at reducere daglig dosis af entecavir oral opløsning, som angivet i tabellen.
A reduction of the daily dose using entecavir oral solution, as detailed in the table, is recommended.
Leverfunktionen skal løbende monitoreres med faste intervaller med såvel klinisk som laboratoriemæssig opfølgning igennem mindst 6 måneder efter seponering af hepatitis B-behandling.
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.
Nyre-clearance er uafhængig af dosis inden for området 360 - 471 ml/min, hvilket tyder på, at entecavir gennemgår såvel glomerulær filtration som net tubulær udskillelse.
Renal clearance is independent of dose and ranges between 360-471 ml/min suggesting that entecavir undergoes both glomerular filtration and net tubular secretion.
Brug af anden medicin sammen med Entecavir Accord
Other medicines and Entecavir Accord
Dosisjustering anbefales hos patienter med kreatinin-clearance < 50 ml/min, inklusive patienter i hæmodialyse eller i vedvarende ambulant peritonealdialyse (CAPD).
Dose adjustment is recommended for patients with creatinine clearance < 50 ml/min, including those on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
Virkningsmekanisme: Entecavir, en guanosinnukleosidanalog med aktivitet mod HBV-polymerase, fosforyleres effektivt til den aktive trifosfat-form (TP), som har en intracellulær halveringstid på 15 timer.
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.
Ved uge 72 efter transplantationen havde ingen af de 55 observerede individer virologisk tilbagefald af HBV [defineret som HBV-DNA ≥50 IE/ml (ca. 300 kopier/ml)], og der var ingen rapporterede virologiske tilbagefald hos de resterende 6 patienter på undersøgelsestidspunktet.
At Week 72 post-transplant, none of 55 observed cases had virologic recurrence of HBV [defined as HBV DNA ≥50 IU/ml (approximately 300 copies/ml)], and there was no reported virologic recurrence at time of censoring for the remaining 6 patients.
I studier med lamivudin-refraktære patienter var den kumulative sandsynlighed for udvikling af genotypisk entecavir-resistens efter 1, 2, 3, 4 og 5 års behandling henholdsvis 6%, 15%, 36%, 47% og 51%.
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.
Køn/alder: Der sås ingen åbenlyse forskelle i sikkerhedsprofil for entecavir med hensyn til køn (≈ 25% kvinder i kliniske forsøg) eller alder (≈ 5% > 65 år).
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).
Efter levertransplantation: Entecavir eksponering hos HBV-inficerede levertransplanterede patienter i behandling med stabil dosis ciclosporin A eller tacrolimus (n = 9) var ≈ 2 gange eksponeringen hos raske frivillige med normal nyrefunktion.
Post-Liver transplant: entecavir exposure in HBV-infected liver transplant recipients on a stable dose of cyclosporine A or tacrolimus (n = 9) was ≈ 2 times the exposure in healthy subjects with normal renal function.
Klinisk erfaring: Påvisning af benefit er baseret på histologisk, virologisk, biokemisk og serologisk respons efter 48 ugers behandling i aktivt kontrollerede kliniske forsøg med 1.633 voksne med kronisk hepatitis B-infektion, dokumenteret virusreplikation og kompenseret leversygdom.
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, evidence of viral replication and compensated liver disease.
Der sås ingen åbenlyse forskelle i effekt af entecavir baseret på køn (≈ 25% kvinder i de kliniske forsøg) eller alder (≈ 5% af patienter var > 65 år).
There was no apparent difference in efficacy for entecavir based on gender (≈ 25% women in the clinical trials) or age (≈ 5% of patients > 65 years of age).
hiv-varianter, der indeholder M184I-substitutionen, viste tab af følsomhed mod entecavir (se pkt.
HIV variants containing the M184V substitution showed loss of susceptibility to entecavir (see section 4.4).
Blisterpakning:
Blister pack:
Kvinder har større risiko for lactacidose, specielt hvis de er meget overvægtige.
Lactic acidosis occurs more often in women, particularly if they are very overweight.
Resistens og specifikke forsigtighedsregler for lamivudin-refraktære patienter: Mutationer i den HBVpolymerase, der koder for lamivudin-resistens-substitutioner, kan forårsage sekundære substitutioner, inklusive entecavir-associerede resistens-substitutioner (ETVr).
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).
Derfor bør kliniske parametre og laboratorieparametre monitoreres tæt hos denne patientpopulation (se også pkt.
Therefore, clinical and laboratory parameters should be closely monitored in this patient population (see also sections 4.8 and 5.1).
Responskriterier var HBV-virologisk suppression (HBV-DNA < 0,7 MEq/ml ved bDNA) og tab af HBeAg (hos HBeAg-positive patienter) eller ALAT < 1,25 gange ULN (hos HBeAg-negative patienter).
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).
Det er vigtigt, fordi Entecavir Accord udskilles gennem nyrerne, og din dosis eller dosisintervallet skal tilpasses.
Entecavir Accord is eliminated from your body through the kidneys and your dose or dosing schedule may need to be adjusted.
Det vides ikke, om fundene er prædiktive for mennesker.
The predictivity of the findings for humans is not known.
HDPE-beholder (high-density polyethylene), indeholdende en silicagelbeholder, med børnesikret polypropylen-lukning der indeholder 30 filmovertrukne tabletter.
High-density polyethylene (HDPE) bottle contians a silica gel cainster with child resistant polypropylene closure containing 30 film-coated tablets.
Patienterne havde et gennemsnitligt CTP-tal på 8,59 ved baseline, og 26% af patienterne var i CTPklasse C. Det gennemsnitlige score for Model for End Stage Liver Disease (MELD) ved baseline var 16,23.
At baseline, patients had a mean CTP score of 8.59 and 26% of patients were CTP class C. The mean baseline Model for End Stage Liver Disease (MELD) score was 16.23.
Integreret analyse af fase 2 og 3 kliniske studier: I en integreret analyse efter markedsføring af entecavir-resistensdata fra 17 fase 2 og 3 kliniske studier blev der fundet en ny entecavirresistensassocieret substitution rtA181C i 5 ud af 1461 forsøgspersoner under behandlingen med entecavir.
Integrated Analysis of Phase 2 and 3 Clinical Studies: In a post-approval integrated analysis of entecavir resistance data from 17 Phase 2 and 3 clinical studies, an emergent entecavir resistanceassociated substitution rtA181C was detected in 5 out of 1461 subjects during treatment with entecavir.
• når risikostyringssystemet ændres, særlig som følge af, at der er modtaget nye oplysninger, der kan medføre en væsentlig ændring i risk/benefit-forholdet, eller som følge af, at en vigtig milepæl (lægemiddelovervågning eller risikominimering) er nået.
An updated RMP should be submitted: At the request of the European Medicines Agency; Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
Den anbefalede dosis til voksne patienter med inkompenseret leversygdom er 1 mg en gang dagligt, som skal tages på tom mave (mere end 2 timer før og mere end 2 timer efter et måltid) (se pkt.
The recommended dose for adult patients with decompensated liver disease is 1 mg once daily, which must be taken on an empty stomach (more than 2 hours before and more than 2 hours after a meal) (see section 5.2).
Præ-eksisterende lamivudin-resistent HBV er associeret med en øget risiko for efterfølgende entecavir-resistens uanset graden af leversygdom; hos patienter med inkompenseret leversygdom kan virologisk svigt være associeret med alvorlige kliniske komplikationer af den underliggende leversygdom.
Pre-existing lamivudine-resistant HBV is associated with an increased risk for subsequent entecavir resistance regardless of the degree of liver disease; in patients with decompensated liver disease, virologic breakthrough may be associated with serious clinical complications of the underlying liver disease.
Ved studiets start var gennemsnitlig HBV-DNA 8,1 log10 IE/ml og gennemsnitlig ALAT var 103 E/l på tværs af studiepopulationen.
At study entry, the mean HBV DNA was 8.1 log10 IU/ml and mean ALT was 103 U/l across the study population.
- genotype-ETVrc med virologisk svigt d
- genotypic ETVrc with virologic breakthrough d
I kliniske studier med patienter med kompenseret leversygdom var de almindeligste bivirkninger af alle sværhedsgrader, og hvor en forbindelse med entecavir var mulig, hovedpine (9 %), træthed (6 %), svimmelhed (4 %) og kvalme (3 %).
In clinical studies in patients with compensated liver disease, 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%).
I forhold til de bivirkninger, der er anført i punkt b. Liste i tabelform over bivirkninger, blev der observeret en yderligere bivirkning [fald i blodhydrogencarbonat (2%)] hos entecavir-behandlede patienter i uge 48.
Relative to the adverse reactions noted in section b. Tabulated list of adverse reactions, one additional adverse reaction [decrease in blood bicarbonate (2%)] was observed in entecavir-treated patients through week 48.
Serum-ALAT skal være vedvarende forhøjet i mindst 6 måneder inden behandling af pædiatriske patienter med kompenseret leversygdom forårsaget af HBeAG-positiv kronisk hepatitis B og i mindst 12 måneder hos patienter med HBeAG-negativ sygdom.
Serum ALT should be persistently elevated for at least 6 months prior to treatment of paediatric patients with compensated liver disease due to HBeAg positive chronic hepatitis B; and for at least 12 months in patients with HBeAg negative disease.
Ældre patienter: Dosisjustering er ikke nødvendig på baggrund af alder.
Elderly: no dosage adjustment based on age is required.
Der er ingen anbefalinger for entecavir til børn under 2 år eller til børn, der vejer mindre end 10 kg.
There are no recommendations for entecavir in children less than 2 years of age or weighing less than 10 kg.