natgillin/translations-raw huggingface dataset:
Nogle patienter har rapporteret om svimmelhed, koncentrationsbesvær og problemer med synet, mens de tager Daklinza sammen med anden medicin mod hepatitis C-infektion.
Some patients have reported dizziness, difficulty concentrating, and vision problems while taking Daklinza with other medicines for their hepatitis C infection.
Grænseværdierne for HCV-RNA, som udløser seponering af behandlingen (dvs. regler for seponering), er vist i tabel 3.
The HCV RNA thresholds that trigger discontinuation of treatment (i.e. treatment stopping rules) are presented in Table 3.
SVR12-raten hos patienter med genotype 3-infektion med denne RAV er nedsat (i praksis recidiv efter respons ved afsluttet behandling), især hos patienter med cirrose.
The SVR12 rate in genotype-3 infected patients with this RAV is reduced (in practice as relapse after end of treatment response), especially in patients with cirrhosis.
Forventes: ↔ Triazolam
Expected: ↔ Triazolam
Ved steady-state var daclatasvirs proteinbinding hos HCV-inficerede patienter ca. 99% og uafhængig af dosis ved det undersøgte dosisområde (1 mg til 100 mg).
At steady state, protein binding of daclatasvir in HCV-infected patients was approximately 99% and independent of dose at the dose range studied (1 mg to 100 mg).
Dosisjustering af Daklinza eller buprenorphin er ikke nødvendig, men det anbefales, at patienterne monitoreres for tegn på opiattoksicitet.
No dose adjustment of Daklinza or buprenorphine may be required, but it is recommended that patients should be monitored for signs of opiate toxicity.
Så længe skal du tage Daklinza Du skal sørge for at tage Daklinza så længe, som din læge har bedt dig om at tage det.
How long to take Daklinza Make sure you take Daklinza for as long as your doctor has told you to take it.
Der foreligger ingen kliniske data for patienter med genotype 5 (se pkt.
There are no clinical data in patients with genotype 5 (see section 5.1).
Fortæl det til lægen, hvis et eller flere af følgende punkter gælder for dig: du får eller inden for de seneste måneder har du fået lægemidlet amiodaron mod uregelmæssig hjerterytme (lægen kan overveje andre behandlinger, hvis du har taget dette lægemiddel) du har eller har haft en infektion med hepatitis B-virus, da din læge måske vil overvåge dig tættere din lever er skadet og virker ikke, som den skal (dekompenseret leversygdom)
Tell your doctor if any of the following applies: you currently take, or have taken in the last few months, the medicine amiodarone to treat irregular heartbeats (your doctor may consider alternative treatments if you have taken this medicine) you have a current or previous infection with the hepatitis B virus, since your doctor may want to monitor you more closely your liver is damaged and not functioning properly (decompensated liver disease)
Patienter med HCV-infektion (uanset genotype) og med høj risiko for dekompensation eller død inden for 12 måneder uden behandling blev behandlet i compassionate use programmer.
Patients with HCV infection (across genotypes) at high risk of decompensation or death within 12 months if left untreated were treated under compassionate use programmes.
Fire patienter seponerede Daklinza på grund af bivirkninger, hvoraf kun en blev vurderet til at være relateret til studiebehandlingen.
Four patients discontinued the Daklinza regimen for adverse events, only one of which was considered related to study therapy.
MÆRKNING, DER SKAL ANFØRES PÅ DEN YDRE EMBALLAGE YDRE KARTONTEKST
PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON TEXT
Produktresuméerne for de andre lægemidler i behandlingen bør ligeledes konsulteres, før behandling med Daklinza initieres.
The Summary of Product Characteristics for the other medicinal products in the regimen should also be consulted before initiation of therapy with Daklinza.
Resistens i cellekulturer
Resistance in cell culture
Demografiske data og baseline-karakteristika for disse 50 patienter var generelt sammenlignelige med demografiske data og baseline-karakteristika for patienter, som fik 12 ugers studiebehandling.
Demographic and baseline characteristics of these 50 patients were generally comparable to those for patients who received 12 weeks of study treatment.
Der blev ikke observeret evidens for mutagen eller clastogen aktivitet i in vitro mutagentest (Ames' test), mutationsprøver i pattedyr i ovarieceller fra kinesiske hamstre eller i et in vivo oralt mikronukleus-studie i rotter.
No evidence of mutagenic or clastogenic activity was observed in in vitro mutagenesis (Ames) tests, mammalian mutation assays in Chinese hamster ovary cells, or in an in vivo oral micronucleus study in rats.
Daklinza er endnu ikke tilstrækkeligt undersøgt hos børn og unge.
Daklinza has not yet been studied in children and adolescents.
In vitro og in vivo studier viste, at daclatasvir er et P-gp-substrat.
In vitro and in vivo studies showed that daclatasvir is a substrate of P-gp.
og du opdager det 20 timer eller mere efter det tidspunkt, hvor du normalt tager Daklinza, skal du vente og tage den næste dosis på det sædvanlige tidspunkt.
and you notice 20 hours or more after the time you usually take Daklinza, wait and take the next dose at your usual time.
De hyppigst rapporterede bivirkninger var træthed, hovedpine og kvalme.
The most frequently reported adverse reactions were fatigue, headache, and nausea.
AUC: 1,05 (1,03; 1,07) Cmax: 1,07 (1,02; 1,12) Cmin: 1,10 (1,03; 1,19)
It may harm them, even if their signs of illness are the same as yours.
Digoxin bør anvendes med forsigtighed ved samtidig administration med Daklinza.
Digoxin should be used with caution when coadministered with Daklinza.
Elimination Efter oral administration af en enkeltdosis på of 14C-daclatasvir til raske forsøgspersoner blev 88% af den totale radioaktivitet genfundet i fæces (53% som uomdannet lægemiddel) og 6,6% blev udskilt i urin (primært som uomdannet lægemiddel).
Elimination Following single-dose oral administration of 14C-daclatasvir in healthy subjects, 88% of total radioactivity was recovered in feces (53% as unchanged drug) and 6.6% was excreted in the urine (primarily as unchanged drug).
Ethinylestradiol 35 μg en gang dagligt i 21 dage + norgestimat
Ethinylestradiol 35 μg once daily for 21 days + norgestimate
For at vurdere recidiv af hepatocellulært karcinom associeret med Daklinza skal indehaveren af markedsføringstilladelsen udføre og indsende resultaterne fra et prospektivt sikkerhedsstudie baseret på en vedtagen protokol med brug af data fra en kohorte af en veldefineret gruppe patienter.
In order to evaluate the recurrence of hepatocellular carcinoma associated with Daklinza, the MAH shall conduct and submit the results of a prospective safety study using data deriving from a cohort of a well-defined group of patients, based on an agreed protocol.
Den sofosbuvir-resistensassocierede substitution S282T opstod kun hos 1 non-SVR12 patient med genotype 3-infektion.
The sofosbuvir resistance-associated substitution S282T emerged in only 1 non-SVR12 patient infected with genotype 3.
Klinisk relevant koncentrationsstigning er angivet med “↑”, og klinisk relevant fald er angivet med “↓”, ingen klinisk relevant ændring er angivet med “↔”.
Clinically relevant increase in concentration is indicated as “↑”, clinically relevant decrease as “↓”, no clinically relevant change as “↔”.
Disse substitutioner medførte lav resistens (EC50 <1 nM) for genotype 1b og højere grad af resistens for genotype 1a (EC50 op til 350 nM).
These substitutions conferred low level resistance (EC50 <1 nM) for genotype 1b, and higher levels of resistance for genotype 1a (EC50 up to 350 nM).
Patienterne bør informeres om at, hvis de glemmer at tage en dosis af Daklinza, skal de tage den så snart de kommer i tanke om det inden for 20 timer fra det planlagte tidspunkt.
Patients should be instructed that, if they miss a dose of Daklinza, the dose should be taken as soon as possible if remembered within 20 hours of the scheduled dose time.
Dosis af daclatasvir blev tilpasset den samtidige antiretrovirale behandling.
The dose of daclatasvir was adjusted for concomitant antiretroviral use.
Daklinza anbefales ikke til børn og unge under 18 år, da sikkerhed og virkning ikke er blevet undersøgt i denne population.
Daklinza is not recommended for use in children and adolescents aged below 18 years because the safety and efficacy have not been established in this population.
Administration af Daklinza kan øge den systemiske eksponering for lægemidler, der er substrater for P-gp, OATP 1B1, OCT1 eller BCRP, hvilket kan øge eller forlænge deres terapeutiske virkning og bivirkninger.
Administration of Daklinza may increase systemic exposure to medicinal products that are substrates of P-gp, OATP 1B1, OCT1 or BCRP, which could increase or prolong their therapeutic effect and adverse reactions.
In vitro hæmmer daclatasvir de renale optagelsestransportere OAT1 og 3 og OCT2, men det forventes ikke at have nogen klinisk effekt på farmakokinetikken hos substraterne for disse transportere.
In vitro daclatasvir is an inhibitor of renal uptake transporters, OAT1 and 3, and OCT2, but is not expected to have a clinical effect on the pharmacokinetics of substrates of these transporters.
SVR12-raterne var lavere hos patienter med cirrose (se Tabel 12).
SVR12 rates were lower among patients with cirrhosis (see Table 12).
Farmakoterapeutisk klassifikation: Direkte virkende antivirale midler, ATC-kode: J05AX14.
Pharmacotherapeutic group: Direct-acting antiviral, ATC code: J05AX14
En omregning af FibroTest score til den tilsvarende METAVIR score indikerer, at 35% af alle patienter (49% af patienterne med tidligere mislykket PI-behandling, 30% af patienterne med genotype 2 eller 3) havde ≥F3 leverfibrose.
Conversion of the FibroTest score to the corresponding METAVIR score suggests that 35% of all patients (49% of patients with prior PI failure, 30% of patients with genotype 2 or 3) had ≥F3 liver fibrosis.
Behandlingsnaive patienter med HCV-genotype 1, som fik 12 ugers behandling, viste lignende respons som de, der blev behandlet i 24 uger (Tabel 6).
Treatment-naïve patients with HCV genotype 1 who received 12 weeks of treatment had a similar response as those treated for 24 weeks (Table 6).
Daclatasvir er en meget svag CYP3A4-hæmmer og medførte en nedsættelse af midazolam eksponering på 13%.
Daclatasvir is a very weak inducer of CYP3A4 and caused a 13% decrease in midazolam exposure.
Langtidsdata
Long term efficacy data
De hyppigst rapporterede bivirkninger af en sværhedsgrad på minimum 3 (hyppighed på 1% eller mere) var neutropeni, anæmi, lymfopeni og trombocytopeni.
The most frequently reported adverse reactions of at least Grade 3 severity (frequency of 1% or greater) were neutropenia, anaemia, lymphopenia and thrombocytopenia.
Farmakokinetiske populationsanalyser af data fra kliniske studier indikerer, at alder ikke havde nogen åbenbar effekt på daclatasvirs farmakokinetik.
Population pharmacokinetic analysis of data from clinical studies indicated that age had no apparent effect on the pharmacokinetics of daclatasvir.
Daclatasvir er en hæmmer af det ustrukturelle protein 5A (NS5A), som er et multifunktionelt protein, der udgør en vigtig del af HCV-replikationskomplekset.
Daclatasvir is an inhibitor of nonstructural protein 5A (NS5A), a multifunctional protein that is an essential component of the HCV replication complex.
Virologisk gennembrud**
Virologic breakthrough**
Regime og behandlingsvarighed HCV-GT 1 eller 4
Regimen and duration HCV GT 1 or 4
Patienten med virologisk gennembrud opfyldte den oprindelige protokoldefinition på bekræftet HCVRNA <LLOQ, detekterbart ved uge 8.
The patient with virologic breakthrough met the original protocol definition of confirmed HCV RNA <LLOQ, detectable at treatment Week 8.
Hvis du holder op med at tage Daklinza
If you stop taking Daklinza
Indigo carmine aluminum lake (E132) Gul jernoxid (E172)
Indigo carmine aluminum lake (E132) Yellow iron oxide (E172)
I kliniske fase 1-studier fik raske forsøgspersoner, som fik op til 100 mg en gang dagligt i op til 14 dage eller enkeltdoser på op til 200 mg, ingen uventede bivirkninger.
In phase 1 clinical studies, healthy subjects who received up to 100 mg once daily for up to 14 days or single doses up to 200 mg had no unexpected adverse reactions.
Tabel over interaktioner
Tabulated summary of interactions
Proteasehæmmere (PI'ere) Boceprevir
Protease inhibitors (PIs) Boceprevir
Administration af daclatasvir 60 mg tablet efter et let måltid medførte ingen reduktion i daclatasvir-eksponering.
Administration of daclatasvir 60 mg tablet after a light meal resulted in no reduction in daclatasvir exposure.
Den aktive transport medieres af OCT1 og andre, uidentificerede optagelsestransportere, men ikke af organisk aniontransporter (OAT) 2, natrium-taurocholat co-transporterende polypeptid (NTCP) eller OATP'er.
The active transport is mediated by OCT1 and other unidentified uptake transporters, but not by organic anion transporter (OAT) 2, sodium-taurocholate cotransporting polypeptide (NTCP), or OATPs.
Mødre skal oplyses om, at de ikke må amme deres barn, hvis de tager Daklinza.
Mothers should be instructed not to breastfeed if they are taking Daklinza.
Hvis du glemmer en dosis: og du opdager det inden for 20 timer efter det tidspunkt, hvor du normalt tager Daklinza, skal du tage tabletten så hurtigt som muligt.
If you do miss a dose: and you notice within 20 hours of the time you usually take Daklinza, you must take the tablet as soon as possible.
ND: Ikke fastlagt
Min, Max ND: Not determined
Der findes ingen kendt antidot mod overdosering af daclatasvir.
There is no known antidote for overdose of daclatasvir.
Substitutioner, der medførte daclatasvir-resistens i genotype 1-4, blev observeret i NS5A's aminosyreregion N-terminal 100 i et cellebaseret replikon-system.
Substitutions conferring daclatasvir resistance in genotypes 1-4 were observed in the N-terminal 100 amino acid region of NS5A in a cell-based replicon system.
Kreatininclearance >50 ml/min
Creatinine Clearance >50 mL/min
Behandlingsvarigheden var 12 uger for 82 behandlingsnaive HCV-genotype 1-patienter og 24 uger for alle andre patienter i studiet.
Treatment duration was 12 weeks for 82 treatment-naïve HCV genotype 1 patients, and 24 weeks for all other patients in the study.
Din læge vil muligvis justere din dosis af Daklinza eller du vil muligvis ikke kunne tage Daklinza sammen med visse typer medicin.
Your doctor may need to adjust the dose of Daklinza or you may not be able to take Daklinza with certain medicines.
Hos patienter med Child-Pugh A, B eller C cirrose eller recidiv af HCV-infektion efter levertransplantation er den anbefalede startdosis af ribavirin 600 mg dagligt sammen med mad.
For patients with Child-Pugh A, B, or C cirrhosis or recurrence of HCV infection after liver transplantation, the recommended initial dose of ribavirin is 600 mg daily with food.
Sikkerhedsmonitorering tilrådes, når behandling med Daklinza initieres hos patienter, der får dabigatranetexilat eller andre intestinale P-gp substrater med et snævert terapeutisk virkningsområde.
Safety monitoring is advised when initiating treatment with Daklinza in patients receiving dabigatran etexilate or other intestinal P-gp substrates that have a narrow therapeutic range.
Der er begrænset erfaring med uforsætlig overdosering af daclatasvir i kliniske studier.
There is limited experience of accidental overdose of daclatasvir in clinical studies.
Samlet set blev SVR12 nået af 97% (149/153) af patienterne, der fik daclatasvir og sofosbuvir i 12 uger i ALLY-2.
Overall, SVR12 was achieved by 97% (149/153) of patients administered daclatasvir and sofosbuvir for 12 weeks in ALLY-2.
Det Europæiske Lægemiddelagentur har udsat forpligtelsen til at fremlægge resultaterne af studier med daclatasvir i en eller flere undergrupper af den pædiatriske population i behandlingen af kronisk hepatitis C (se pkt.
The European Medicines Agency has deferred the obligation to submit the results of studies with daclatasvir in one or more subsets of the paediatric population in the treatment of chronic hepatitis C (see section 4.2 for information on paediatric use).
Behandlingsresultaterne fra studie AI444042 er vist i tabel 13.
Treatment outcomes in study AI444042 are presented in Table 13.
* Undersøgt hos opioidafhængige voksne i stabil vedligeholdelsesbehandling med methadon.
* Evaluated in opioid-dependent adults on stable methadone maintenance therapy.
Tabel 10: Demografiske data og baseline-karakteristika i ALLY-2-studiet
Table 10: Demographics and baseline characteristics in Study ALLY-2
Alle patienter, som får Daklinza og sofosbuvir i kombination med amiodaron med eller uden andre hjertefrekvenssænkende lægemidler, skal ligeledes advares om symptomerne på bradykardi og hjerteblok og tilrådes at søge øjeblikkelig lægehjælp, hvis de kommer ud for dem.
All patients receiving Daklinza and sofosbuvir in combination with amiodarone with or without other drugs that lower heart rate should also be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.
For HCV-genotype 1 var SVR12 raterne 64% (54% for 1a; 84% for 1b) for patienter, der blev behandlet med daclatasvir + pegIFN/RBV og 36% for patienter, der blev behandlet med placebo + pegIFN/RBV.
For HCV genotype 1, SVR12 rates were 64% (54% for 1a; 84% for 1b) for patients treated with daclatasvir + pegIFN/RBV and 36% for patients treated with placebo + pegIFN/RBV.
Seponering af peginterferon alfa og ribavirin (behandling med Daklinza er komplet ved uge 24)
Discontinue peginterferon alfa and ribavirin (treatment with Daklinza is complete at week 24)
Observeret opståen af NS5A-resistensassocierede varianter er vist i tabel 14.
Observed emergent NS5A resistance-associated variants are reported in Table 14.
Daklinza skal altid anvendes sammen med anden medicin mod hepatitis C-infektion og må aldrig anvendes alene.
Daklinza must always be used together with other medicines against hepatitis C infection and must never be used by itself.
Forholdet mellem de geometriske middelværdier er vist med 90% konfidensinterval (KI) i parenteser, hvor det er muligt.
If available, ratios of geometric means are shown, with 90% confidence intervals (CI) in parentheses.
I en undersøgelse af den præ- og postnatale udvikling i rotter, forekom der hverken maternel eller udviklingsmæssig toksicitet ved doser på op til 50 mg/kg/dag associeret med AUC-værdier 2 gange højere end klinisk AUC-eksponering.
In a study of pre- and postnatal development in rats, there was neither maternal nor developmental toxicity at doses up to 50 mg/kg/day, associated with AUC values 2-fold the clinical AUC exposure.
Graviditet Der foreligger ingen data om anvendelse af daclatasvir til gravide kvinder.
There are no data from the use of daclatasvir in pregnant women.
Patienter, som havde manglende data ved opfølgningsuge 12, blev betragtet som responderende patienter, hvis deres næste tilgængelige HCV-RNA værdi var <LLOQ.
Patients who had missing data at follow-up Week 12 were considered responders if their next available HCV RNA value was <LLOQ.
Data fra compassionate use programmer, som inkluderer patienter med genotype 3-infektion og cirrose, understøtter anvendelse af Daklinza + sofosbuvir i 24 uger til disse patienter.
Data from compassionate use programmes which included patients with genotype 3 infection and cirrhosis, support the use of Daklinza + sofosbuvir for 24 weeks in these patients.
Det er ukendt, om daclatasvir udskilles i human mælk.
It is not known whether daclatasvir is excreted in human milk.
Studie udført med patienter med kronisk HCV-infektion
Study conducted in patients with chronic HCV infection
Daclatasvir EC50-værdierne i replikonsystemet var 0,003-1,25 nM for genotype 3a, 4a, 5a og 6a og 0,034-19 nM for genotype 2a samt 0,020 nM for infektiøs genotype 2a (JFH-1) virus.
The daclatasvir EC50 values in the replicon system were 0.003-1.25 nM for genotypes 3a, 4a, 5a and 6a, and 0.034-19 nM for genotype 2a as well as 0.020 nM for infectious genotype 2a (JFH-1) virus.
In vitro og in vivo studier viser, at daclatasvir er substrat for CYP3A, idet CYP3A4 er den vigtigste CYP-isoform og ansvarlig for metabolismen.
In vitro and in vivo studies demonstrate that daclatasvir is a substrate of CYP3A, with CYP3A4 being the major CYP isoform responsible for the metabolism.
Fusionshæmmer Enfuvirtid
Fusion inhibitor Enfuvirtide
Polyvinylchlorid/polychlortrifluorethylen(PVC/PCTFE) klart blister/aluminum folielåg.
Polyvinyl Chloride/poly-chloro-tri-fluoro-ethylene (PVC/PCTFE) clear blister/aluminum foil lidding.
Indvirkningen af NS5A-RAV'er ved baseline på helbredelsesraterne for genotype 4-infektion er ikke åbenbar.
The impact of baseline NS5A RAVs on cure rates of genotype 4 infection is not apparent.
Studier med daclatasvir hos dyr har vist embryotoksiske og teratogene virkninger (se pkt.
Studies of daclatasvir in animals have shown embryotoxic and teratogenic effects (see section 5.3).
SVR12-rater var højere for patienter med IL-28B CC-genotypen end for dem med non-CC genotyper og for patienter med HCV-RNA under 800,000 IU/ml ved baseline men konsekvent højere hos daclatasvir-behandlede patienter end hos placebo-behandlede patienter i alle undergrupper.
SVR12 rates were higher for patients with the IL-28B CC genotype than for those with non-CC genotypes and for patients with baseline HCV RNA less than 800,000 IU/ml but consistently higher in the daclatasvir-treated patients than for placebo-treated patients in all subgroups.
L31V og Y93H var hyppigt observerede resistenssubstitutioner i genotype 1b, mens M28T, L31V/M, Q30E/H/R og Y93C/H/N var hyppigt observerede resistenssubstitutioner i genotype 1a.
L31V and Y93H were frequently observed resistance substitutions in genotype 1b, while M28T, L31V/M, Q30E/H/R, and Y93C/H/N were frequently observed resistance substitutions in genotype 1a.
Hvis det er nødvendigt at afbryde behandlingen med andre behandlingskomponenter på grund af bivirkninger, må Daklinza ikke gives som monoterapi.
If treatment interruption of components in the regimen is necessary because of adverse reactions, Daklinza must not be given as monotherapy.
Hvis de imidlertid først kommer i tanke om den glemte dosis mere end 20 timer efter det planlagte tidspunkt, skal de springe den over og tage den næste dosis på det planlagte tidspunkt.
However, if the missed dose is remembered more than 20 hours after the scheduled dose, the dose should be skipped and the next dose taken at the appropriate time.
↔ Daclatasvir ↔ Immunosuppresiva
↔ Daclatasvir ↔ Immunosuppressant
I kliniske studier med Daklinza i kombination med sofosbuvir med eller uden ribavirin oplevede 2% af patienterne fald i hæmoglobin grad 3; alle disse patienter fik Daklinza + sofosbuvir + ribavirin.
In clinical studies of Daklinza in combination with sofosbuvir with or without ribavirin, 2% of patients had Grade 3 haemoglobin decreases; all of these patients received Daklinza + sofosbuvir + ribavirin.
SVR12 blev nået hos 83% (50/60) af patienterne i cirrosekohorten med en markant forskel mellem patienter med Child-Pugh A eller B (92-94%) sammenlignet med patienter med Child-Pugh C og 94% af patienterne i kohorten, der havde gennemgået en levertransplantation (tabel 9).
SVR12 was achieved by 83% (50/60) of patients in the cirrhosis cohort, with a marked difference between patients with Child-Pugh A or B (92-94%) as compared to those with Child-Pugh C and 94% of patients in the post-liver transplant cohort (Table 9).
Den anbefalede dosis af Daklinza er 60 mg en gang dagligt.
The recommended dose of Daklinza is 60 mg once a day.
Opståede daclatasvir-resistensassocierede substitutioner er vist at persistere i 2 år efter afsluttet behandling og endnu længere hos patienter, der blev behandlet med andre daclatasvir-baserede regimer.
Emergent daclatasvir resistance-associated substitutions have been shown to persist for 2 years posttreatment and beyond for patients treated with other daclatasvir-based regimens.
Hvis du er i den fødedygtige alder, skal du bruge sikker prævention under og 5 uger efter behandlingen med Daklinza.
If you can become pregnant, use effective contraception during and for 5 weeks after your treatment with Daklinza.