natgillin/translations-raw huggingface dataset:
For at differentiere mellem stigninger i aminotransferaser på grund af respons på behandling og stigninger, der kan være forbundet med lactacidose, bør lægen sikre sig, at stigningerne i ALAT er forbundet med forbedringer i andre laboratoriemarkører for kronisk hepatitis B.
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.
Mutationer i den HBV- polymerase, 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).
ETVr- substitutioner er set ved segment rtT184, rtS202 eller rtM250 ved baseline.
In a small percentage of lamivudine-refractory patients, ETVr substitutions at residues rtT184, rtS202 or rtM250 were present at baseline.
Patienter med lamivudin- resistent HBV har højere risiko for efterfølgende at udvikle entecavir- resistens end patienter, der ikke er lamivudin - resistente.
Patients with lamivudine-resistant HBV are at higher risk of developing subsequent entecavir resistance than patients without lamivudine resistance.
Den kumulative sandsynlighed for udvikling af genotypisk entecavir- resistens efter 1, 2, 3, 4 og 5 års behandling i undersøgelser af lamivudin- resistens var 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.
Virologisk respons skal monitoreres hyppigt i den lamivudin- refraktoriske population, og der skal udføres relevant resistenstest.
Virological response should be frequently monitored in the lamivudine-refractory population and appropriate resistance testing should be performed.
4. 5 og 5. 1).
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).
Der er begrænsede data vedrørende effekt og sikkerhed af entecavir til levertransplanterede patienter.
Liver transplant recipients: there are limited data on efficacy and safety of entecavir in liver transplant recipients.
5. 2).
Renal function should be carefully evaluated before and during entecavir therapy in liver transplant recipients receiving cyclosporine or tacrolimus (see section 5.2).
Der er ingen data vedrørende effekt af entecavir hos patienter, der samtidigt er inficerede med hepatitis C - eller D- virus.
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.
4 Human immundefekt virus (HIV) / HBV- inficererede patienter som ikke samtidig får antiretroviral behandling:
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
Entecavir er ikke blevet evalueret hos HIV/ HBV- inficerede patienter, som ikke samtidig får effektiv HIV- behandling.
4 concurrently receiving effective HIV treatment.
Fremkomsten af HIV- resistens er set, når entecavir blev anvendt til behandling af kronisk hepatitis B- infektion hos patienter med HIV- infektion, som ikke fik antiretroviral kombinationsbehandling (highly active antiretroviral therapy - HAART) (se pkt.
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).
Behandling med entecavir bør derfor ikke anvendes til HIV/ HBV- inficerede patienter, som ikke får HAART.
Therefore, therapy with entecavir should not be used for HIV/ HBV co-infected patients who are not receiving HAART.
Entecavir er ikke blevet undersøgt til behandling af HIV- infektion og frarådes til dette brug.
Entecavir has not been studied as a treatment for HIV infection and is not recommended for this use.
5. 1).
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).
Der foreligger ingen data vedrørende effekten af entecavir hos HBeAg - negative patienter med samtidig HIV- infektion.
No data are available on the efficacy of entecavir in HBeAg-negative patients co-infected with HIV.
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).
Patienterne skal informeres om, at det ikke er påvist, at behandling med entecavir mindsker risikoen for overførsel af HBV, og at der derfor fortsat skal tages relevante forholdsregler.
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.
Dette lægemiddel indeholder 120, 5 mg lactose i hver 0, 5 mg daglig dosis.
Lactose: this medicinal product contains 120.5 mg of lactose in each 0.5 mg daily dose.
Patienter med sjældne, arvelige problemer med galaktose- intolerans, Lapp laktasemangel eller glukose- galaktose malabsorption bør ikke tage denne medicin.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
5. 2), kan samtidig administration med præparater, der reducerer nyrefunktionen eller konkurrerer med hensyn til aktiv tubulær udskillelse, forøge serumkoncentrationen af de respektive præparater.
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.
Bortset fra lamivudin, adefovirdipivoxil - og tenofovirdisoproxilfumarat er effekten ved samtidig administration af entecavir og præparater, der udskilles gennem nyrerne eller påvirker nyrefunktionen, ikke evalueret.
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.
Hvis entecavir administreres samtidig med sådanne præparater, bør patienten monitoreres tæt for uønskede hændelser.
Patients should be monitored closely for adverse reactions when entecavir is coadministered with such medicinal products.
5. 2).
Entecavir is not a substrate, an inducer or an inhibitor of cytochrome P450 (CYP450) enzymes (see section 5.2).
CYP450- medierede lægemiddelinteraktioner med entecavir er derfor ikke sandsynlige.
Therefore CYP450 mediated drug interactions are unlikely to occur with entecavir.
5. 3).
Studies in animals have shown reproductive toxicity at high doses (see section 5.3).
Ud fra den betragtning, at risikoen for fostre er ukendt, bør fertile kvinder anvende effektiv antikonception.
Given that the potential risks to the developing foetus are unknown, women of child-bearing potential should use effective contraception.
Det vides ikke, om entecavir udskilles i modermælk.
It is unknown whether entecavir is excreted in human breast milk.
Dyrestudier har vist, at entecavir udskilles i mælken hos dyr.
Animal studies have shown excretion of entecavir in breast milk.
Amning kan ikke anbefales under behandling med Baraclude.
Breastfeeding is not recommended during treatment with Baraclude.
På baggrund af entecavirs farmakodynamiske profil, forventes disse aktiviteter ikke
No effect on such activities is expected based on the pharmacodynamic profile of entecavir.
Svimmelhed, voldsom træthed og søvnighed er hyppige bivirkninger, som kan påvirke evnen til at føre motorkøretøj og betjene maskiner.
Dizziness, fatigue and somnolence are common side effects which may impair the ability to drive and use machines.
4. 8 Bivirkninger
5 4.8 Undesirable effects
Vurdering af bivirkninger er baseret på 4 kliniske forsøg, hvor 1. 720 patienter med kronisk hepatitis B infektion fik dobbeltblind behandling med entecavir 0, 5 mg/ dag (n = 679), entecavir 1 mg/ dag (n = 183) eller lamivudin (n = 858) i op til 107 uger.
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.
Sikkerhedsprofilen for entecavir og lamivudin, inklusiv laboratorietest- abnormaliteter, var sammenlignelig i disse forsøg.
The safety profiles of entecavir and lamivudine, including laboratory test abnormalities, were comparable in these studies.
De mest almindelige bivirkninger som optrådte i en hvilken som helst sværhedsgrad, og hvor forbindelse med entecavir var mulig, var hovedpine (9%), træthed (6%), svimmelhed (4%) og kvalme (3%).
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%).
Bivirkninger, der som minimum vurderedes 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.
Hyppighed defineres som meget almindelig (≥ 1/ 10); almindelig ≥ 1/ 100, < 1/ 10).
Frequency is defined as very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10).
Erfaring hos patienter der ikke tidligere har været behandlet med nukleosid (HBeAg- positive og - negative):
Experience in nucleoside naive patients (HBeAg positive and negative):
Sikkerhedsprofilen er baseret på indtag af entecavir 0, 5 mg, én gang dagligt i gennemsnitligt 53 uger.
The safety profile is based on treatment exposure to entecavir 0.5 mg once daily for a median of 53 weeks.
Almene lidelser og reaktioner på indgivelsesstedet:
General disorders and administration site conditions:
Laboratorietest- abnormaliteter:
Laboratory test abnormalities:
2% af patienterne havde ALAT- stigninger både > 10 gange den øvre normalgrænse (ULN) og > 2 gange baseline; 5% havde ALAT- stigninger > 3 gange baseline; < 1% havde ALAT- stigninger > 2 gange baseline sammen med total- bilirubin > 2 gange ULN og > 2 gange baseline.
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.
Der sås albuminniveauer < 2, 5 g/ dl hos < 1% af patienterne, amylaseniveauer > 3 gange baseline hos 2%, lipaseniveauer > 3 gange baseline hos 11% samt trombocytter < 50. 000/ mm3 hos < 1%.
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%.
Fortsat behandling med entecavir, med en gennemsnitlig varighed på 96 uger, har ikke rejst nye sikkerhedsspørgsmål.
Treatment beyond 48 weeks: continued treatment with entecavir for a median duration of 96 weeks did not reveal any new safety signals.
Erfaring med lamivudin- refraktoriske patienter:
Experience in lamivudine-refractory patients:
Sikkerhedsprofilen er baseret på behandling med entecavir 1 mg, én gang dagligt, i gennemsnitligt 69 uger.
The safety profile is based on treatment exposure to entecavir 1 mg once daily for a median of 69 weeks.
meget almindelig: hovedpine almindelig: svimmelhed, søvnighed
very common: headache common: dizziness, somnolence
6 Laboratorietest- abnormaliteter:
Laboratory test abnormalities:
2% af patienterne havde ALAT- stigninger både > 10 gange ULN og > 2 gange baseline; 4% havde ALAT- stigninger > 3 gange baseline; < 1% havde ALAT- stigninger > 2 gange baseline sammen med total- bilirubin > 2 gange ULN og > 2 gange baseline.
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.
Der sås amylaseniveauer > 3 gange baseline hos 2% af patienterne, lipaseniveauer > 3 gange baseline hos 18% og trombocytter < 50. 000/ mm3 hos < 1%.
Amylase levels > 3 times baseline occurred in 2% of patients, lipase levels > 3 times baseline in 18% and platelets < 50,000/ mm3 in < 1%.
Behandling ud over 48 uger: fortsat behandling med entecavir, med en gennemsnitlig varighed på 96 uger, har ikke rejst nye sikkerhedsspørgsmål.
6 Treatment beyond 48 weeks: continued treatment with entecavir for a median duration of 96 weeks did not reveal any new safety signals.
I studier med patienter, der ikke tidligere har været behandlet med nukleosid, sås under behandling ALAT- stigninger > 10 gange ULN og > 2 gange baseline hos 2% af de entecavir- behandlede patienter vs 4% af de lamivudin- behandlede patienter.
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.
I studier med lamivudin- refraktoriske patienter sås under behandling ALAT- stigninger > 10 gange ULN og > 2 gange baseline hos 2% af entecavir- behandlede patienter vs 11% af lamivudin- behandlede patienter.
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.
Stigningerne svandt generelt ved fortsat behandling og de var, i de fleste tilfælde, forbundet med en ≥ 2 log10/ ml reduktion i viral load, der gik forud for eller faldt sammen med ALAT- stigningen.
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.
4. 4).
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).
I studier med patienter, der ikke tidligere er behandlet med nukleosid oplevede 6% af de entecavir- behandlede patienter og 10% af de lamivudin- behandlede patienter ALAT- stigninger (> 10 gange ULN og > 2 gange referenceværdien [mindst af baseline eller sidste måling ved afslutning af behandling]) ved opfølgning efter behandling.
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.
Blandt entecavir- behandlede patienter, der ikke tidligere var behandlet med nukleosid, var den gennemsnitlige tid til ALAT- stigning 23 - 24 uger, og 86% (24/ 28) af ALAT- stigningerne opstod hos HBeAg- negative patienter.
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.
I studier med lamivudin - refraktoriske patienter, hvor kun et begrænset antal patienter blev fulgt op, udviklede 11% af de entecavir- behandlede patienter og ingen af de lamivudin- behandlede patienter ALAT- stigninger under opfølgning efter behandling.
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.
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.
4. 4).
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).
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).
Der er set højere forekomst af alvorlige leverbivirkninger hos patienter med inkompenseret cirrhose sammenlignet med patienter med kompenseret leverfunktion.
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.
Udover de bivirkninger som er fundet i kliniske forsøg er den følgende bivirkning fundet under anvendelse af entecavir efter markedsføring.
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.
Frekvens ukendt: udslæt
frequency not known: rash
I tilfælde af overdosis
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.
7 skal patienten monitoreres for tegn på toksicitet og gives understøttende standardbehandling efter behov.
If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.
Farmakoterapeutisk klassifikation: nukleosid og nukleotidreverstranskriptase- hæmmer ATC- kode:
Pharmacotherapeutic group: nucleoside and nucleotide reverse transcriptase inhibitors
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 at konkurrere med det naturlige substrat deoxyguanosin- TP, hæmmer entecavir- TP funktionelt de 3 aktiviteter af den virale polymerase:
By competing with the natural substrate deoxyguanosine TP, entecavir-TP functionally inhibits the 3 activities of the viral polymerase:
(1) priming af HBV- polymerase, (2) revers - transkription af den negative streng DNA fra det prægenome messenger- RNA og (3) syntese af den positive streng HBV- DNA.
(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.
Entecavir- TP Ki for HBV DNA polymerase er 0, 0012 μM.
The entecavir-TP Ki for HBV DNA polymerase is 0.0012 μ M.
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.
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).
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.
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).
Rekombinante, virakodende for adefovir- resistente substitutioner ved rtN236T eller rtA181V forblev fuldt følsomme over for entecavir.
Recombinant viruses encoding adefovir-resistant substitutions at either rtN236T or rtA181V remained fully susceptible to entecavir.
De laveste EC50- værdier blev observeret, når reducerede niveauer af virus blev anvendt i analysen.
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.
I cellekulturer, valgte entecavir, en M184I- substitution i mikromolære koncentrationer, hvilket beviste inhibitorisk aktivitet ved høje entecavir- koncentrationer.
In cell culture, entecavir selected for an M184I substitution at micromolar concentrations, confirming inhibitory pressure at high entecavir concentrations.
4. 4).
HIV variants containing the M184V substitution showed loss of susceptibility to entecavir (see section 4.4).
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.
I antivirale HIV- assays var entecavir i mikromolære koncentrationer ikke antagonistisk over for anti- HIV- aktivitet i cellekulturer af disse 6 NRTI' er eller emtricitabin.
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.
I forhold til vild- type HBV, viste LVDr vira indeholdende rtM204V - og rtL180M- substitutioner inden for den reverse transkriptase 8 gange mindre følsomhed over for entecavir.
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.
Indlemmelse af yderligere ETVr- aminosyreforandringer rtT184, rtS202 eller rtM250 medfører fald i entecavirfølsomhed i cellekulturer.
Incorporation of additional ETVr amino acid changes rtT184, rtS202 or rtM250 decreases entecavir susceptibility in cell culture.
Substitutioner observeret i kliniske isolater (rtT184A, C, F, G, I, L, M eller S; rtS202 C, G eller I; og/ eller rtM250I, L eller V) reducerede yderligere entecavirfølsomheden 16 til 741 gange i forhold til vild- type virus.
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.
ETVr- substitutioner ved restkoncentration rtT184, rtS202 og rtM250 alene, har kun beskeden effekt på entecavirfølsomheden og er i mere end 1000 behandlede patientprøver ikke observeret ved fravær af LVDr- substitutioner.
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.
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.