natgillin/translations-raw huggingface dataset:
Da kreatin fosfokinase er et enzym, som forhøjes ved muskelskader, skal lægen nøje overvåge alle muskelrelaterede bivirkninger.
Because creatine phosphokinase is an enzyme that is raised when muscles are damaged, doctors need to monitor all muscle-related side effects closely.
Den fuldstændige liste over alle de indberettede bivirkninger ved Sebivo fremgår af indlægssedlen.
For the full list of all side effects reported with Sebivo, see the Package Leaflet.
Sebivo bør ikke anvendes til personer, som kan være overfølsomme (allergiske) over for telbivudin eller et af de øvrige indholdsstoffer.
Sebivo should not be used in people who may be hypersensitive (allergic) to telbivudine or to any of the other ingredients.
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at fordelene ved Sebivo er større end risiciene ved behandling af kronisk hepatitis B hos voksne patienter med kompenseret leversygdom og med tegn på aktiv viral replikation, vedvarende forhøjede serum - alaninaminotransferase (ALAT) - niveauer og histologiske tegn på aktiv leverbetændelse og/ eller – fibrose.
The Committee for Medicinal Products for Human Use (CHMP) decided that Sebivo’ s benefits are greater than its risks for the treatment of chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication, persistently elevated serum ALT levels and histological evidence of active inflammation and/ or fibrosis.
Da undersøgelserne hovedsagelig er foretaget i Asien og omfattede færre kaukasiske patienter, end udvalget kunne have ønsket, bad udvalget virksomheden om at foretage en yderligere undersøgelse i Europa.
As the studies were mainly carried out in Asia and included fewer Caucasian patients than the Committee would have liked to see, the Committee asked the company to carry out a further study in Europe.
Udvalget anbefalede udstedelse af markedsføringstilladelse for Sebivo.
The Committee recommended that Sebivo be given marketing authorisation.
Andre oplysninger om Sebivo:
Other information about Sebivo:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Sebivo til Novartis Europharm Limited den 24. april 2007.
The European Commission granted a marketing authorisation valid throughout the European Union for Sebivo to Novartis Europharm Limited on 24 April 2007.
Den fuldstændige EPAR for Sebivo findes her.
The full EPAR for Sebivo can be found here.
EU- nummer EU/ 1/ 07/ 388/ 001 EU/ 1/ 07/ 388/ 002
EU Number EU/ 1/ 07/ 388/ 001 EU/ 1/ 07/ 388/ 002
Særnavn Sebivo Sebivo
Invented name Sebivo Sebivo
Styrke 600 mg 600 mg
Strength 600 mg 600 mg
Lægemiddelform Filmovertrukket tablet Filmovertrukket tablet
Pharmaceutical Form Film-coated tablet Film-coated tablet
Emballage Blister (PVC/ alu) Blister (PVC/ alu)
Packaging Blister (PVC/ alu) Blister (PVC/ alu)
Paknings- størrelse 28 tabletter 98 tabletter
Package size 28 tablets 98 tablets
1 flaske + 1 kop
1 bottle + 1 Cup
Hver filmovertrukken tablet indeholder 600 mg telbivudine.
Each film-coated tablet contains 600 mg telbivudine.
Hvid til svagt gullig, oval filmovertrukken tablet, præget med ” LDT ” på den ene side.
White to slightly yellowish, oval film-coated tablet, imprinted with “ LDT” on one side.
Se pkt.
Sebivo is indicated for the treatment of chronic hepatitis B in adult patients with compensated liver disease and evidence of viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/ or fibrosis.
5. 1 for detaljer om den kliniske undersøgelse og de specifikke patientkarakteristika, som denne indikation er baseret på.
See section 5.1 for details of the study and specific patient characteristics on which this indication is based.
Behandlingen skal indledes af en læge med erfaring i behandling af kronisk hepatitis B- infektion.
Therapy must be initiated by a physician experienced in the management of chronic hepatitis B infection.
Voksne Den anbefalede dosis Sebivo er 600 mg (1 tablet) 1 gang dagligt, taget oralt med eller uden mad.
Adults The recommended dose of Sebivo is 600 mg (one tablet) once daily, taken orally, with or without food.
Behandlingsophør skal overvejes i følgende situationer: • Hos HBeAg- positive patienter uden cirrose skal behandlingen mindst gives i 6- 12 måneder efter HBe- serokonvertering (clearing af HBeAg og HBV- DNA med påvisning af anti- HBe) er bekræftet eller indtil HBs- serokonvertering eller der er bevis for ophør af effekt.
Treatment discontinuation should be considered as follows: • In HBeAg-positive patients without cirrhosis, treatment should be administered for at least 6-12 months after HBe seroconversion (HBeAg loss and HBV DNA loss with anti-HBe detection) is confirmed or until HBs seroconversion or there is evidence of loss of efficacy.
Serum ALT og HBV DNA- niveauer bør overvåges regelmæssigt efter afslutning af behandlingen for at bestemme ethvert virologisk tilbagefald. • Hos HBeAg- negative patienter uden cirrose skal behandlingen mindst gives indtil HBs - serokonvertering, eller indtil der er tegn på ophør af effekt.
Serum ALT and HBV DNA levels should be followed regularly after treatment discontinuation to detect any late virological relapse. • In HBeAg-negative patients without cirrhosis, treatment should be administered at least until HBs seroconversion or until there is evidence of loss of efficacy.
5. 1) og kan være brugbar for at styre overvågningen af patienter behandlet med telbivudinmonoterapi.
On-treatment response at week 24 has been shown to be predictive of longer-term response (see Table 7 in section 5.1) and might be useful for driving the management of patients treated with telbivudine monotherapy.
2 Nedsat nyrefunktion Justering af den anbefalede dosis af telbivudin er ikke nødvendig hos patienter, hvis kreatininclearance er ≥ 50 ml/ min.
2 Renal impairment No adjustment of the recommended dose of telbivudine is necessary in patients whose creatinine clearance is ≥ 50 ml/ min.
Justering af dosis er påkrævet hos patienter med kreatininclearance < 50 ml/ min, herunder patienter med nyresygdom i slutstadiet (end- stage renal disease (ESRD)) i hæmodialyse.
Adjustment of the dose is required in patients with creatinine clearance < 50 ml/ min, including those with end-stage renal disease (ESRD) on haemodialysis.
Justering af doseringsregime for Sebivo hos patienter med nedsat nyrefunktion
Dosing regimen adjustment of Sebivo in patients with renal impairment
Telbivudin 20 mg/ ml oral opløsning Daglig dosisjustering
Telbivudine 20 mg/ ml oral solution Daily dose adjustment
Telbivudin 600 mg filmovertrukne tabletter Alternativ ** dosisjustering med øgede doseringsintervaller
Telbivudine 600 mg film-coated tablet Alternative** dose adjustment with increased dose intervals
≥ 50 30- 49 < 30 (kræver ikke dialyse)
≥ 50 30-49 < 30 (not requiring dialysis)
600 mg (30 ml) 1 gang dagligt 400 mg (20 ml) 1 gang dagligt 200 mg (10 ml) 1 gang dagligt
600 mg (30 ml) once daily 400 mg (20 ml) once daily 200 mg (10 ml) once daily
600 mg 1 gang dagligt 600 mg 1 gang hver 48. time 600 mg 1 gang hver 72. time
600 mg once daily 600 mg once every 48 hours 600 mg once every 72 hours
* End stage renal disease (nyresygdom i slutstadiet) ** Hvis anvendelse af oral opløsning ikke er muligt.
* End stage renal disease ** In case use of the oral solution is not possible
De foreslåede dosismodifikationer er baseret på ekstrapolation, og det er derfor ikke sikkert, de er optimale.
The safety and effectiveness of these dosing adjustment guidelines have not been clinically evaluated.
Sikkerhed og effekt af disse retningslinjer for doseringsjustering er ikke vurderet klinisk, hvorfor tæt klinisk monitorering hos disse patienter anbefales.
Therefore, close clinical monitoring is recommended in these patients.
5. 2).
End-stage renal disease patients For patients with ESRD, Sebivo should be administered after haemodialysis (see section 5.2).
5. 2).
Hepatic impairment No adjustment to the recommended dose of Sebivo is necessary in patients with hepatic impairment (see section 5.2).
Børn og unge Sebivo bør ikke anvendes til børn og unge under 16 år p. g. a. manglende dokumentation for sikkerhed og virkning.
Children and adolescents Sebivo is not recommended for use in children and adolescents below 16 years of age due to a lack of data on safety and efficacy.
4. 4).
Elderly patients (age above 65 years) No data are available to support a specific dose recommendation for patients over the age of 65 years (see section 4.4).
Svære akutte eksacerbationer af kronisk hepatitis B er relativt hyppige og karakteriseres ved forbigående forhøjelse af serum- ALT.
Severe acute exacerbations of chronic hepatitis B are relatively frequent, and are characterised by transient elevation of serum ALT.
4. 8).
Following initiation of antiviral treatment, serum ALT may rise in some patients while serum levels of HBV DNA fall (see section 4.8).
I gennemsnit gik der 4- 5 uger, før der forekom en eksacerbation hos de patienter, der fik behandling med telbivudin.
On average, 4-5 weeks elapsed prior to the occurrence of an exacerbation in patients treated with telbivudine.
Forhøjede ALT - niveauer forekom hyppigere hos HBeAg- positive patienter end hos HBeAg- negative patienter.
Overall, ALT flares occurred more frequently in HBeAg-positive patients than in HBeAg-negative patients.
Risikoen for
In patients with compensated liver disease, this elevation of serum ALT is generally not accompanied by elevated levels of serum bilirubin or by other signs of hepatic decompensation.
3 leverinkompensation – og for en efterfølgende eksacerbation af hepatiten – kan være forhøjet hos patienter med cirrose.
The risk of hepatic decompensation – and of a subsequent exacerbation of hepatitis – may be elevated in patients with cirrhosis.
Hepatitiseksacerbationer er også beskrevet hos patienter, som har afsluttet behandling af hepatitis B.
3 Exacerbations of hepatitis have also been reported in patients who have terminated treatment of hepatitis B.
Forhøjede ALT- niveauer efter afsluttet behandling er normalt forbundet med forhøjelser i serum - HBV- DNA- niveau, og hovedparten af disse tilfælde har vist sig at være selvbegrænsende.
Post-treatment ALT flares are normally associated with increases in serum HBV DNA levels, and the majority of such cases have proven to be self-limiting.
Ikke desto mindre er der også indberettet svære – og undertiden fatale – sygdoms- eksacerbationer efter behandlingen.
Nonetheless, there have also been reports of severe – and sometimes fatal – post-treatment disease exacerbations.
Leverfunktionen skal derfor monitoreres med regelmæssige intervaller med både klinisk og laboratoriemæssig opfølgning i mindst 6 måneder efter ophør med hepatitis B- behandling.
Therefore, hepatic function should be monitored at regular intervals with both clinical and laboratory follow-up for at least 6 months after discontinuation of hepatitis B therapy.
Forekomst af laktatacidose (med fravær af hypoxæmi), undertiden fatal, og i reglen i forbindelse med svær hepatomegali med steatose, er blevet indberettet ved brug af nukleosid - / nukleotidanaloger.
Occurrence of lactic acidosis (in the absence of hypoxaemia) sometimes fatal, and usually associated with severe hepatomegaly with steatosis have been reported with the use of nucleoside/ nucleotide analogues.
Behandling med nukleosidanaloger skal seponeres, hvis der forekommer hurtigt stigende aminotransferaseniveauer, progressiv hepatomegali eller metabolisk acidose/ laktatacidose 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.
Svære tilfælde, undertiden med fatal udgang, var forbundet med pankreatitis, leverinsufficiens/ leversteatose, nyreinsufficiens og høje koncentrationer af serumlaktat.
Severe cases, sometimes with fatal outcome, were associated with pancreatitis, liver failure/ hepatic steatosis, renal failure and higher levels of serum lactate.
4. 8).
Muscular effects Cases of myopathy and myalgia have been reported with telbivudine use several weeks to months after starting therapy (see section 4.8).
Myopati, defineret som persisterende uklarlagte muskelsmerter og/ eller nedsat muskelkraft, skal uanset graden af stigninger i kreatinkinaseniveauer overvejes hos enhver patient med diffuse uforklarede myalgier, muskelømhed, nedsat muskelkraft eller myositis (defineret som myopati med histologisk evidens af muskelskade).
Myopathy, defined as persistent unexplained muscle aches and/ or muscle weakness regardless of the degree of increases in creatine kinase levels, should be considered in any patient with diffuse unexplained myalgias, muscle tenderness, muscle weakness or myositis (defined as myopathy with histological evidence of muscle damage).
Det vides ikke, om risikoen for myopati under behandling med telbivudin er forhøjet ved samtidig indgivelse af andre lægemidler, der forbindes med myopati (f. eks. statiner, fibrater eller ciclosporin).
It is not known whether the risk of myopathy during treatment with telbivudine is increased with concurrent administration of other medicinal products associated with myopathy (e. g. statins, fibrates, or ciclosporin).
Perifer neuropati Hos patienter, der er behandlet med telbivudin, er perifer neuropati blevet rapporteret med frekvensen ikke almindelig.
Peripheral neuropathy Peripheral neuropathy has been uncommonly reported in telbivudine-treated patients.
4. 8).
If peripheral neuropathy is suspected, treatment with telbivudine should be reconsidered (see section 4.8).
4. 5).
An increased risk of peripheral neuropathy has been observed when telbivudine and pegylated interferon alfa-2a are co-administered (see section 4.5).
En sådan øget risiko kan ikke udelukkes for andre interferon- alfa (pegyleret eller standard).
Such increased risk cannot be excluded for other interferons alfa (pegylated or standard).
Derudover er fordelene ved denne kombination af telbivudin med interferon alfa (pegyleret eller standard) ikke fastslået på nuværende tidspunkt.
Moreover, the benefit of this combination of telbivudine with interferon alfa (pegylated or standard) is not currently established.
Justering af dosisinterval anbefales derfor hos patienter med kreatininclearance < 50 ml/ min, herunder patienter i hæmodialyse.
Renal function Telbivudine is eliminated primarily by renal excretion, therefore dose interval adjustment is recommended in patients with creatinine clearance < 50 ml/ min, including patients on haemodialysis.
4. 2 og 5. 2).
Therefore, virological response should be closely monitored in patients with increased dosage interval (see sections 4.2 and 5.2).
3% af de inkluderede patienter havde cirrose), skal telbivudin anvendes med særlig forsigtighed hos patienter med cirrose.
4 Patients with cirrhosis without decompensation Due to the limited data available (about 3% of patients enrolled had cirrhosis), telbivudine should be used with particular caution in cirrhotic patients.
Patienter med cirrose med dekompensation Der er ingen effekt - eller sikkerhedsdata for patienter med dekompenseret cirrose.
Patients with cirrhosis with decompensation There are no efficacy and safety data in patients with decompensated cirrhosis.
Patienter med antiviralresistent HBV- infektion De tilgængelig data støtter ikke brugen af telbivudin monoterapi til patienter med fastslået lamivudin - resistent hepatitis B- virus- infektion.
Patients with antiviral resistant HBV infection Available evidence does not support the use of telbivudine monotherapy in patients with established lamivudine-resistant hepatitis B virus infection.
In vitro var telbivudin ikke aktivt mod HBV- stammer indeholdende rtM204V/ rtL180M eller rtM204I mutationer (se pkt.
In vitro, telbivudine was not active against the HBV strains containing rtM204V/ rtL180M or rtM204I mutations (see section 5.1).
I kliniske undersøgelser er der ikke påvist en effekt af telbivudin mod HBV med M204V- mutationen.
The efficacy of telbivudine against HBV harbouring the M204V mutation has not been established in clinical trials.
Der foreligger ingen data vedr. telbivudin behandling til patienter med påvist adefovir- resistent hepatitis B- virus enkeltmutationer af rtN236T eller A181V.
There are no data on telbivudine treatment in patients with established adefovir-resistant hepatitis B virus single mutations of rtN236T or A181V.
Præliminære resultater fra cellebaserede analyser viste, at adefovir- resistensassocieret substitution A181V havde 3, 7 gange reduceret følsomhed for telbuvidin.
The preliminary results from the cell-based assay showed that the adefovir resistance-associated substitution A181V had 3.7 fold reduced susceptibility to telbivudine.
I pivotalstudiet var graden af genotypisk verificeret telbivudin- resistens 2, 7% efter 48 uger.
The rate of genotypically confirmed telbivudine resistance in the pivotal study at 48 weeks was 2.7%.
Levertransplantatrecipienter Man har ingen viden om telbivudins sikkerhed og effekt hos levertransplantatrecipienter.
Liver transplant recipients The safety and efficacy of telbivudine in liver transplant recipients are unknown.
Ældre patienter Kliniske undersøgelser af telbivudin omfattede ikke et tilstrækkeligt antal patienter ≥ 65 år til at afgøre, om denne patientgruppe responderer anderledes end yngre personer.
Elderly patients Clinical studies of telbivudine did not include sufficient numbers of patients ≥ 65 years of age to determine whether they respond differently from younger subjects.
I betragtning af den højere frekvens af nedsat nyrefunktion forårsaget af samtidig sygdom eller samtidig brug af andre lægemidler skal der generelt udvises forsigtighed, når Sebivo ordineres til ældre patienter.
In general, caution must be exercised when prescribing Sebivo to elderly patients in view of the greater frequency of decreased renal function due to concomitant disease or concomitant use of other medicinal products.
Andre specielle populationer Sebivo er ikke blevet undersøgt hos co- inficerede hepatitis B- patienter (f. eks. patienter, der er co - inficerede med humant immundefektvirus [HIV], hepatitis C- virus [HCV] eller hepatitis D- virus [HDV]).
Other special populations Sebivo has not been investigated in co-infected hepatitis B patients (e. g. patients co-infected with human immunodeficiency virus [HIV], hepatitis C virus [HCV] or hepatitis D virus [HDV]).
Generelt Patienterne skal informeres om, at det ikke er påvist, at Sebivo reducerer risikoen for overførsel af HBV til andre ved seksuel kontakt eller blodkontaminering.
General Patients should be advised that treatment with Sebivo has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.
Telbivudin bør ikke bruges sammen med lamivudin, da det behandlingsrespons, der blev observeret for kombinationsterapi med telbivudin og lamivudin i en fase II- undersøgelse, var lavere end med telbivudin alene.
Telbivudine is not recommended to be used with lamivudine because in a phase II study, the treatment response observed with combination therapy of telbivudine and lamivudine was lower than with telbivudine alone.
Der er på nuværende tidspunkt ingen effekt - og sikkerhedsdata for andre antivirale kombinationer med telbivudin.
There are currently no efficacy and safety data for other antiviral combinations with telbivudine.
Da telbivudin primært elimineres vha. renal udskillelse, kan samtidig administration af Sebivo og stoffer, som påvirker nyrefunktionen (så som aminoglykosider, loop- diuretika, platinpræparater, vancomycin, amphotericin B), påvirke plasmakoncentrationerne af telbivudin og/ eller det samtidigt administrerede stof.
Since telbivudine is eliminated primarily by renal excretion, co-administration of Sebivo with substances that affect renal function (such as aminoglycosides, loop diuretics, platinum compounds, vancomycin, amphotericin B) may affect plasma concentrations of telbivudine and/ or the co- administered substance.
Telbivudins farmakokinetik ved steady- state var uændret efter multidosisadministration i kombination med lamivudin, adefovir, dipivoxil, tenofovirdisoproxilfumarat, ciclosporin eller pegyleret interferon alfa- 2a.
The steady-state pharmacokinetics of telbivudine were unaltered following multiple dose administration in combination with lamivudine, adefovir dipivoxil, tenofovir disoproxil fumarate, ciclosporin or pegylated interferon alfa-2a.
5 vedrørende telbivudins virkninger på det pegylerede interferons farmakokinetik på grund af høj interindividuel koncentrationsvariabilitet for pegyleret interferon alfa- 2a.
No definitive conclusion could be drawn regarding the effects of telbivudine on the pharmacokinetics of pegylated 5 interferon due to high interindividual variability of pegylated interferon alfa-2a concentrations.
Et klinisk studie, der undersøger kombinationen af telbivudin 600 mg daglig og pegyleret interferon alfa- 2a, 180 mikrogram én gang ugentlig ved subkutan administration indikerer, at kombinationen er forbundet med en øget risiko for at udvikle perifer neuropati.
A clinical trial investigating the combination of telbivudine, 600 mg daily, with pegylated interferon alfa-2a, 180 micrograms once weekly by subcutaneous administration, indicates that this combination is associated with an increased risk of developing peripheral neuropathy.
4. 4).
The mechanism behind these events is not known (see section 4.4).
Potentialet for CYP450- medierede lægemiddelinteraktioner, der involverer Sebivo, er derfor lille.
Telbivudine is not a substrate, inhibitor or inducer of the cytochrome P450 (CYP450) enzyme system (see section 5.2). Therefore, the potential for CYP450-mediated drug interactions involving Sebivo is low.
Der foreligger ingen kliniske data om eksponering for telbivudin under graviditet.
For telbivudine no clinical data on exposed pregnancies are available.
Forsøg med drægtige rotter og kaniner viste, at telbivudin passerer placenta.
Studies in pregnant rats and rabbits showed that telbivudine crosses the placenta.
Forsøg med drægtige kaniner viste tidlig fødsel og/ eller abort sekundært til maternel toksicitet.
Studies in pregnant rabbits showed early delivery and/ or abortion secondary to maternal toxicity.
Der forefindes ingen data vedr. telbivudins virkning på overførsel af HBV fra mor til barn.
There are no data on the effect of telbivudine on transmission of HBV from mother to infant.
Der skal derfor tages hensigtsmæssige forholdsregler for at undgå neonatal erhvervelse af HBV- infektion.
Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV infection.
Det vides ikke, om telbivudin udskilles i human modermælk.
It is not known whether telbivudine is excreted in human milk.
Kvinder må ikke amme, hvis de tager Sebivo.
Women should not breast-feed if they are taking Sebivo.
14 gange højere end dem, der sås hos mennesker på den terapeutiske dosis.
In reproductive toxicology studies, no evidence of impaired fertility was seen in male or female rats at systemic exposures approximately 14 times those observed in humans at the therapeutic dose.
Vurderingen af bivirkninger er hovedsageligt baseret på to studier (NV- 02B- 007 ” GLOBE ” og NV - 02B- 015), hvor 1. 699 patienter med kronisk hepatitis B fik behandling med telbivudin 600 mg/ dag (n = 847) eller lamivudin (n = 852) i 104 uger.
Assessment of adverse reactions is mainly based on two studies (NV-02B-007 “ GLOBE” and NV- 02B-015) in which 1,699 patients with chronic hepatitis B received double-blind treatment with telbivudine 600 mg/ day (n = 847) or lamivudine (n = 852) for 104 weeks.
De indberettede bivirkninger i de kliniske undersøgelser af 104 ugers varighed blev sædvanligvis klassificeret som milde eller moderate i sværhedsgrad.
In the 104-week clinical studies, reported adverse reactions were usually classified as mild or moderate in severity.