natgillin/translations-raw huggingface dataset:
De langsigtede konsekvenser af disse hændelser er p. t. ikke kendte.
The long-term consequences of these events are currently
Viden om mekanismen er ufuldstændig.
Knowledge about the mechanism is incomplete.
En hypotese om forbindelsen mellem visceral lipomatose og proteasehæmmere samt lipoatrophia og nukleosid reverse transkriptasehæmmere er blevet opstillet.
A connection between visceral lipomatosis and protease inhibitors, and lipoatrophy and nucleoside reverse transcriptase inhibitors has been hypothesised.
En højere risiko for lipodystrophia er blevet forbundet med individuelle faktorer som f. eks. højere alder, og med lægemiddelrelaterede faktorer som f. eks. længere varighed af antiretroviral behandling og associererede metaboliske forstyrrelser.
A higher risk of lipodystrophy has been associated with individual factors such as older age, and with drug related factors such as longer duration of antiretroviral treatment and associated metabolic disturbances.
Klinisk undersøgelse bør omfatte evaluering af fysiske tegn på omfordeling af fedt.
Clinical examination should include evaluation for physical signs of fat redistribution.
Lipidændringer bør behandles på klinisk relevant måde.
Lipid disorders should be managed as clinically appropriate.
Patienter med tidligere forekommende leverdysfunktion herunder kronisk aktiv hepatitis har en øget frekvens af leverfunktionsabnormiteter under antiretroviral kombinationsbehandling og bør overvåges i henhold til normal praksis.
Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
Hos patienter med kronisk hepatitis B eller C, som behandles med antiretroviral kombinationsbehandling, er der en øget risiko for svære og potentielt fatale, hepatiske uønskede hændelser.
Patients with chronic hepatitis B or C infection treated with combination antiretroviral therapy are at increased risk of experiencing severe, and potentially fatal, hepatic adverse events.
Patienter, som samtidig er inficerede med hepatitis B virus (HBV):
Patients co-infected with hepatitis B virus (HBV):
Der foreligger imidlertid begrænsede data om effekten og sikkerheden af emtricitabin (som en 200 mg hård kapsel én gang daglig) hos patienter, som samtidig er inficerede med HIV og HBV.
However, limited data are available on the efficacy and safety of emtricitabine (as a 200 mg hard capsule once daily) in patients who are co-infected with HIV and HBV.
Brug af emtricitabin hos patienter med kronisk HBV- infektion forårsager det samme mutationsmønster i YMDD- motivet, som ses ved behandling med lamivudin.
The use of emtricitabine in patient with chronic HBV induces the same mutation pattern in the YMDD motif observed with lamivudine therapy.
YMDD- mutationen medfører resistens over for både emtricitabin og lamivudin.
The YMDD mutation confers resistance to both emtricitabine and lamivudine.
Patienter, som samtidig er inficerede med HIV og HBV, bør overvåges nøje med både klinisk og laboratorisk opfølgning i mindst flere måneder, efter behandlingen med emtricitabin ophører, for tegn på eksacerbationer af hepatitis.
Patients co-infected with HIV and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with emtricitabine for evidence of exacerbations of hepatitis.
Sådanne eksacerbationer er set efter emtricitabinbehandlingens ophør hos HBV- inficerede patienter uden ledsagende HIV- infektion og er blevet påvist primært ved stigninger i serum- alanin- amino- transferase (ALAT) samt fremkomst af HBV DNA igen.
Such exacerbations have been seen following discontinuation of emtricitabine treatment in HBV infected patients without concomitant HIV infection and have been detected primarily by serum alanine aminotransferase (ALT) elevations in addition to re-emergence of HBV DNA.
Nukleosid - og nukleotidanaloger har vist sig at forårsage varierende grad af skade på mitokondrier in vitro og in vivo.
Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage.
Disse hændelser er ofte kortvarige.
These events are often transitory.
I hvilken udstrækning de neurologiske forstyrrelser er kortvarige eller permanente er p. t. ikke kendt.
Whether the neurological disorders are transient or permanent is currently unknown.
Alle børn, der har været eksponeret for nukleosid - og nukleotidanaloger in utero, herunder også HIV- negative børn, bør have en klinisk og laboratorisk opfølgning og udredes fuldstændigt med henblik på mulig mitokondriel dysfunktion i tilfælde af relevante tegn eller symptomer.
Any child exposed in utero to nucleoside and nucleotide analogues, even HIV negative children, should have clinical and laboratory follow-up and should be fully investigated for possible mitochondrial dysfunction in case of relevant signs or symptoms.
Hos HIV- inficerede patienter med svær immuninsufficiens kan der ved påbegyndelse af antiretroviral kombinationsbehandling (CART) opstå en inflammatorisk reaktion på asymptomatiske eller residuale opportunistiske patogener, som kan forårsage alvorlige kliniske tilstande eller forværring af symptomer.
In HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
5 generaliserede og/ eller fokale mycobakterielle infektioner og pneumocystis carinii pneumoni.
Relevant examples are cytomegalovirus retinitis, generalised and/ or focal mycobacterium infections, and Pneumocystis carinii pneumonia.
Der er rapporteret om tilfælde af osteonekrose hos patienter, der har fremskreden HIV- sygdom og/ eller hos patienter som befinder sig i langvarig kombinationsbehandling med antiretrovirale lægemidler (CART).
Although the etiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV-disease and/ or long-term exposure to
Ætiologien anses dog for at være multifaktoriel (omfattende anvendelse af kortikosteroider, alkoholforbrug, svær immunosuppression, højere Body Mass Index (BMI)).
5 combination antiretroviral therapy (CART).
In vitro hæmmede emtricitabin ikke metabolisme medieret af en af de følgende humane CYP450 - isoformer:
In vitro, emtricitabine did not inhibit metabolism mediated by any of the following human CYP450 isoforms:
1A2, 2A6, 2B6, 2C9, 2C19, 2D6 og 3A4.
1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4.
Emtricitabin hæmmede ikke det enzym, som er ansvarligt for glucuronidation.
Emtricitabine did not inhibit the enzyme responsible for glucuronidation.
Baseret på resultaterne af disse in vitro forsøg og emtricitabins kendte eliminationsveje er potentialet for CYP450- medierede interaktioner mellem emtricitabin og andre lægemidler lavt.
Based on the results of these in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP450 mediated interactions involving emtricitabine with other medicinal products is low.
Derfor kan anvendelsen af emtricitabin i kombination med lamivudin eller zalcitabin til behandlingen af HIV- infektion ikke anbefales på nuværende tidspunkt.
Consequently, the use of emtricitabine in combination with lamivudine or zalcitabine for the treatment of HIV infection cannot be recommended at this time.
Sikkerheden af emtricitabin under graviditet er ikke godtgjort.
The safety of emtricitabine in human pregnancy has not been established.
5. 3).
Animal studies do not indicate direct or indirect harmful effects of emtricitabine with respect to pregnancy, foetal development, parturition or postnatal development (see section 5.3).
Emtricitabin bør kun anvendes på tvingende indikation til gravide.
Emtricitabine should be used during pregnancy only if necessary.
Da de potentielle risici for menneskefostre under udvikling er ukendte, skal anvendelse af emtricitabin til kvinder i den fertile alder ledsages af brug af sikker kontraception.
Given that the potential risks to developing human foetuses are unknown, the use of emtricitabine in women of childbearing potential must be accompanied by the use of effective contraception.
Det vides ikke, om emtricitabin udskilles i human modermælk.
It is not known if emtricitabine is excreted in human milk.
For at undgå overførsel af HIV anbefales det, at HIV- inficerede kvinder under ingen omstændigheder ammer deres børn.
It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Vurderingen af bivirkninger er baseret på data fra tre undersøgelser med voksne (n=1. 479) og tre pædiatriske undersøgelser (n=169).
Assessment of adverse reactions is based on data from three studies in adults (n=1,479) and three paediatric studies (n=169).
I undersøgelserne med voksne modtog 1. 039 behandlingsnaive og 440 behandlingserfarne patienter emtricitabin (n=814) eller et referencepræparat (n=665) i 48 uger i kombination med andre antiretrovirale lægemidler.
In the adult studies, 1,039 treatment-naïve and 440 treatment-experienced patients received emtricitabine (n=814) or comparator medicinal product (n=665) for 48 weeks in combination with other antiretroviral medicinal products.
I tre pædiatriske undersøgelser fik behandlingsnaive (n=123) og behandlingserfarne (n=46) pædiatriske patienter fra i alderen fra 4 måneder til 18 år behandling med emtricitabin i kombination med andre antiretrovirale midler.
In three paediatric studies, treatment-naïve (n=123) and treatment-experienced (n=46) paediatric patients aged 4 months to 18 years were treated with emtricitabine in combination with other antiretroviral agents.
Bivirkningerne med mistænkt (eller i det mindste en mulig) forbindelse med behandlingen af voksne er anført nedenfor efter legemssystemorganklasse og absolut hyppighed.
6 The adverse reactions with suspected (at least possible) relationship to treatment in adults are listed below by body system organ class and absolute frequency.
Hyppigheder er defineret som meget almindelige (≥ 1/ 10), almindelige (≥ 1/ 100 til < 1/ 10) eller ikke almindelige (≥ 1/ 1. 000 til < 1/ 100).
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10) or uncommon (≥ 1/ 1,000, < 1/ 100).
Almindelig: neutropeni Ikke almindelig: anæmi
Common: neutropenia Uncommon: anaemia
Almindelig: hypertriglyceridæmi, hyperglykæmi
Common: hypertriglyceridaemia, hyperglycaemia
4. 4).
Lactic acidosis, usually associated with hepatic steatosis, has been reported with the use of nucleoside analogues (see section 4.4).
Almindelig: insomnia, unormale drømme
Common: insomnia, abnormal dreams
Meget almindelig: hovedpine Almindelig: svimmelhed
Very common: headache Common: dizziness
Meget almindelig: diarré, kvalme Almindelig: opkastning, mavepine, forhøjet amylase, herunder forhøjet pancreatisk amylase, forhøjet serum- lipase, dyspepsi
Very common: diarrhoea, nausea Common: vomiting, abdominal pain, elevated amylase including elevated pancreatic amylase, elevated serum lipase, dyspepsia
Almindelig: hyperbilirubinæmi, forhøjet serum- aspartat- amino- transferase (ASAT) og/ eller forhøjet serum- alanin- amino- transferase (ALAT)
Common: hyperbilirubinaemia, elevated serum aspartate aminotransferase (AST) and/ or elevated serum alanine aminotransferase (ALT)
Almindelig: allergisk reaktion, urticaria, udslæt med blærer, pustuløst udslæt, macula papel udslæt, pruritus, udslæt og misfarvning af huden (øget pigmentdannelse)
Common: allergic reaction, urticaria, vesiculobullous rash, pustular rash, maculopapular rash, pruritus, rash, and skin discolouration (hyper-pigmentation)
Meget almindelig: forhøjet kreatinkinase
Very common: elevated creatine kinase
Almindelig: asteni, smerter
Common: asthenia, pain
Ud over bivirkninger rapporteret hos voksne var anæmi almindelig og misfarvning af huden (øget pigmentdannelse) meget almindelig hos pædiatriske patienter.
In addition to the adverse reactions reported in adults, anaemia was common and skin discolouration (hyper-pigmentation) was very common in paediatric patients.
Som
The adverse reaction profile in patients co-infected with HBV is similar to that observed in patients infected with HIV without co-infection with HBV.
7 det kunne forventes hos denne patientpopulation, indtrådte stigninger i ASAT og ALAT dog hyppigere end i den generelle HIV- inficerede population.
However, as would be expected in this patient population, elevations in AST and ALT occurred more frequently than in the general HIV infected population.
Antiretroviral kombinationsbehandling er blevet forbundet med omfordeling af legemsfedt (lipodystrophia) hos HIV- patienter herunder tab af perifert og fascialt subkutant fedt, forøget intra- abdominalt og visceralt fedt, hypertrophia mammae og dorsocervical fedtakkumulering (bøffelnakke) (se pkt.
Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal
4. 4).
7 and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump) (see section 4.4).
4. 8).
Administration of up to 1,200 mg emtricitabine has been associated with the adverse reactions listed above (see section 4.8).
Såfremt der forekommer overdosering, skal patienten overvåges for tegn på toksicitet, og der skal gives støttende standardbehandling efter behov.
If overdose occurs, the patient should be monitored for signs of toxicity and standard supportive treatment applied as necessary.
Det vides ikke, om emtricitabin kan fjernes ved peritoneal dialyse.
It is not known whether emtricitabine can be removed by peritoneal dialysis.
Nukleosid og nukleotid reverse transkriptasehæmmere, ATC- kode:
Nucleoside and nucleotide reverse transcriptase inhibitors, ATC code:
Emtricitabin er en syntetisk nukleosidanalog af cytidin med aktivitet, som er specifik mod human immundefekt virus (HIV- 1 og HIV- 2) og hepatitis B virus (HBV).
Emtricitabine is a synthetic nucleoside analogue of cytidine with activity that is specific to human immunodeficiency virus (HIV-1 and HIV-2) and hepatitis B virus (HBV).
Emtricitabin fosforyleres af celleenzymer til at danne emtricitabin 5 '- trifosfat, som kompetitivt hæmmer HIV- 1 reverse transkriptase, som resulterer i DNA- kædeterminering.
Emtricitabine is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate, which competitively inhibits HIV-1 reverse transcriptase, resulting in DNA chain termination.
Emtricitabin er en svag hæmmer af mammalian DNA- polymerase α, β og ε og mitokondriel DNA- polymerase γ.
Emtricitabine is a weak inhibitor of mammalian DNA polymerase α, β and ε and mitochondrial DNA polymerase γ.
Emtricitabin udviste ikke cytotoksicitet over for mononukleære celler i perifert blod (PBMC' er), etablerede lymfocyt - og monocyt- makrofagcellelinier eller knoglemarvsstamceller in vitro.
Emtricitabine did not exhibit cytotoxicity to peripheral blood mononuclear cells (PBMCs), established lymphocyte and monocyte-macrophage cell lines or bone marrow progenitor cells in vitro.
Den koncentration af emtricitabin, som er nødvendig for 50% hæmning (IC50) af laboratoriemæssige og kliniske isolater af HIV- 1, lå inden for området 0, 0013- 0, 5 µmol/ l.
The 50% inhibitory concentration (IC50) value for emtricitabine against laboratory and clinical isolates of HIV-1 was in the range of 0.0013 to 0.5 µmol/ l.
I kombinationsundersøgelser af emtricitabin med proteasehæmmere, nukleosid, nukleotid og non- nukleoside analoghæmmere af HIV- reverse transkriptase, desuden oberserveredes virkninger fra additiv til synergetisk.
In combination studies of emtricitabine with protease inhibitors, nucleoside, nucleotide and non-nucleoside analogue inhibitors of HIV reverse transcriptase, additive to synergistic effects were observed.
8 Ved afprøvning for aktivitet mod laboratoriestammer af HBV lå koncentrationen af emtricitabin for 50% hæmning (IC50) inden for området 0, 01- 0, 04 µmol/ l.
When tested for activity against laboratory strains of HBV, the 50% inhibitory concentration (IC50) value for emtricitabine was in the range of 0.01 to 0.04 µmol/ l.
HIV- 1 resistens over for emtricitabin udvikles som følge af ændringer ved codon 184, som bevirker, at methioninen omdannes til en valin (en intermediær isoleucin er også blevet observeret) af HIV- reverse transkriptase.
HIV-1 resistance to emtricitabine develops as the result of changes at codon 184 causing the methionine to be changed to a valine (an isoleucine intermediate has also been observed) of the HIV reverse transcriptase.
Denne HIV- 1 mutation blev observeret in vitro og hos HIV- 1 inficerede patienter.
This HIV-1 mutation was observed in vitro and in HIV-1 infected patients.
Emtricitabin- resistente virus var krydsresistente over for lamivudin, men beholdt følsomhed over for andre nukleosid reverse transkriptasehæmmere (Nucleoside Reverse Transcriptase Inhibitors, NRTIs) (zidovudin, stavudin, tenofovir, abacavir, didanosin og zalcitabin), alle non- nukleoside reverse transkriptasehæmmere (Non- Nucleoside Reverse Transcriptase Inhibitors, NNRTIs) og alle proteasehæmmere (Protease Inhibitors, PIs).
Emtricitabine-resistant viruses were cross-resistant to lamivudine, but retained sensitivity to other nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine, stavudine, tenofovir, abacavir,
Virus, som var resistente over for zidovudin, zalcitabin, didanosin og NNRTIs, beholdt deres følsomhed over for emtricitabin (IC50=0, 002 µmol/ l- 0, 08 µmol/ l).
8 didanosine and zalcitabine), all non-nucleoside reverse transcriptase inhibitors (NNRTIs) and all protease inhibitors (PIs).
Emtricitabin i kombination med andre antiretrovirale midler, herunder nukleosidanaloger, non- nukleosidanaloger og proteasehæmmere har vist sig at være effektive ved behandlingen af HIV- infektion hos behandlingsnaive patienter og behandlingserfarne patienter med stabil, virologisk kontrol.
Emtricitabine in combination with other antiretroviral agents, including nucleoside analogues, non-nucleoside analogues and protease inhibitors, has been shown to be effective in the treatment of HIV infection in treatment-naïve patients and treatment-experienced patients with stable virological control.
Hos antiretroviral- behandlingsnaive voksne var emtricitabin signifikant bedre end stavudin, når begge lægemidler blev taget i kombination med didanosin og efavirenz gennem 48 ugers behandling.
In antiretroviral treatment-naïve adults, emtricitabine was significantly superior to stavudine when both medicinal products were taken in combination with didanosine and efavirenz through 48 weeks of treatment.
Fenotypeanalyse viste ingen signifikante ændringer i emtricitabindisposition, medmindre der var udviklet M184V/ I mutation.
Phenotypic analysis showed no significant changes in emtricitabine susceptibility unless the M184V/ I mutation had developed.
Hos virologisk stabile, behandlingserfarne voksne viste det sig, at emtricitabin, i kombination med en NRTI (enten stavudin eller zidovudin) og proteasehæmmer (PI) eller en NNRTI ikke var mindre effektiv end lamivudin med hensyn til procentdelen af responderende (< 400 kopier/ ml) i 48 uger (77% emtricitabin, 82% lamivudin).
In virologically stable treatment-experienced adults, emtricitabine, in combination with an NRTI (either stavudine or zidovudine) and a protease inhibitor (PI) or an NNRTI was shown to be non-inferior to lamivudine with respect to the proportion of responders (< 400 copies/ ml) through 48 weeks (77% emtricitabine, 82% lamivudine).
Endvidere i et andet forsøg blev behandlingserfarne voksne på et stabilt PI- baseret, højt aktivt, antiretroviralt behandlingsregime (HAART) randomiseret til et regime med én daglig dosis af emtricitabin eller til at fortsætte med deres PI- HAART regime.
Additionally, in a second study, treatment-experienced adults on a stable PI based highly active antiretroviral therapy (HAART) regimen were randomised to a once daily regimen containing emtricitabine or to continue with their PI-HAART regimen.
Efter 48 ugers behandling viste regimet med emtricitabin en tilsvarende procentdel af patienter med HIV RNA < 400 kopier/ ml (94% emtricitabin versus 92%) og en større procentdel af patienter med HIV RNA < 50 kopier/ ml (95% emtricitabin versus 87%) sammenlignet med de patienter, som fortsatte med deres PI- HAART regime.
At 48 weeks of treatment the emtricitabine-containing regimen demonstrated an equivalent proportion of patients with HIV RNA < 400 copies/ ml (94% emtricitabine versus 92%) and a greater proportion of patients with HIV RNA < 50 copies/ ml (95% emtricitabine versus 87%) compared with the patients continuing with their PI-HAART regimen.
Hos børn, der var over 4 måneder gamle, opnåede eller opretholdt størstedelen af patienterne komplet suppression af plasma HIV- 1 RNA igennem 48 uger (89% opnåede ≤ 400 kopier/ ml og 77% opnåede ≤ 50 kopier/ ml).
In infants and children older than 4 months, the majority of patients achieved or maintained complete suppression of plasma HIV-1 RNA through 48 weeks (89% achieved ≤ 400 copies/ ml and 77% achieved ≤ 50 copies/ ml).
Efter oral indgivelse absorberes emtricitabin hurtigt og omfattende, hvor peak - plasmakoncentrationer opnås 1- 2 timer efter dosering.
Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations occurring at 1 to 2 hours post-dose.
Hos 20 HIV- inficerede forsøgspersoner, som fik 200 mg emtricitabin daglig som hårde kapsler, var de maksimale steady- state emtricitabinkoncentrationer (Cmax) i plasma, de minimale koncentrationer (Cmin) og området under plasmakoncentrationens tidskurve over et 24- timers doseringsinterval (AUC) henholdsvis 1, 8±0, 7 µg/ ml, 0, 09±0, 07 µg/ ml og 10, 0±3, 1 µg· t/ ml.
In 20 HIV infected subjects receiving 200 mg emtricitabine daily as hard capsules, steady-state plasma emtricitabine peak concentrations (Cmax), trough concentrations (Cmin) and area under the plasma concentration time curve over a 24-hour dosing interval (AUC) were 1.8±0.7 µg/ ml, 0.09±0.07 µg/ ml and 10.0±3.1 µg·h/ ml, respectively.
4 gange så høje som in vitro IC90 værdierne for anti- HIV- aktivitet.
Steady-state trough plasma concentrations reached levels approximately 4-fold above the in vitro IC90 values for anti-HIV activity.
9 Den absolutte biotilgængelighed af emtricitabin fra Emtriva 200 mg hårde kapsler blev vurderet til at være 93%, og den absolutte biotilgængelighed fra Emtriva 10 mg/ ml oral opløsning blev vurderet til at være 75%.
The absolute bioavailability of emtricitabine from Emtriva 200 mg hard capsules was estimated to be 93% and the absolute bioavailability from Emtriva 10 mg/ ml oral solution was estimated to be 75%.
80% af biotilgængeligheden af Emtriva 200 mg hårde kapsler.
In a pilot study in children and a definitive bioequivalence study in adults, the Emtriva 10 mg/ ml oral solution was shown to have approximately 80% of the bioavailability of the Emtriva 200 mg hard capsules.
Indtagelse af Emtriva 200 mg hårde kapsler sammen med et måltid med højt fedtindhold eller indtagelse af Emtriva 10 mg/ ml oral opløsning sammen med et måltid med lavt eller højt fedtindhold påvirkede ikke emtricitabins systemiske eksponering (AUC0- ∞); derfor kan Emtriva 200 mg hårde kapsler og Emtriva 10 mg/ ml oral opløsning indtages med eller uden mad.
Administration of Emtriva 200 mg hard capsules with a high-fat meal or administration of Emtriva 10 mg/ ml oral solution with a low-fat or high-fat meal did not affect systemic exposure (AUC0-∞) of emtricitabine; therefore Emtriva 200 mg hard capsules and Emtriva 10 mg/ ml oral solution may be administered with or without food.
Fordeling:
9 Distribution: