natgillin/translations-raw huggingface dataset:
Konsultér produktresuméet for atazanavir eller darunavir for yderligere oplysninger om anvendelse i kombination med disse lægemidler. 
Consult the Summary of Product Characteristics of atazanavir or darunavir for further information on use in combination with these medicinal products.
Behandling med cobicistat og darunavir under graviditeten medfører lavere eksponering for darunavir, hvilket kan være forbundet med en øget risiko for virologisk svigt og en øget risiko for overførsel af hiv-infektion fra mor til barn. 
Treatment with cobicistat and darunavir during pregnancy results in lower darunavir exposure which may be associated with an increased risk of virological failure and an increased risk of mother-to-child transmission of HIV infection.
For yderligere oplysninger om bivirkninger ved atazanavir eller darunavir, se disse lægemidlers indlægssedler. 
For more information on the side effects of atazanavir or darunavir see the package leaflets for these medicines.
Cobicistat er en selektiv, mekanisme baseret hæmmer af cytokromer P450 fra CYP3A-undergruppen. 
Cobicistat is a selective, mechanism-based inhibitor of cytochromes P450 of the CYP3A subfamily.
Patienterne blev randomiseret i et 1:1 forhold til at modtage enten atazanavir 300 mg + cobicistat 150 mg én gang dagligt eller atazanavir 300 mg + ritonavir 100 mg én gang dagligt, begge administreret med en fastdosis-behandlingsplan, der indeholdt tenofovirdisoproxilfumarat 300 mg og emtricitabin 200 mg administreret som en fastdosis-kombinationstablet. 
Patients were randomised in a 1:1 ratio to receive either atazanavir 300 mg + cobicistat 150 mg once daily or atazanavir 300 mg + ritonavir 100 mg once daily, each administered with a fixed background regimen containing tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg administered as a fixed-dose combination tablet.
Hæmning af CYP3A-medieret metabolisme af cobicistat øger den systemiske eksponering over for CYP3A-substrater (såsom atazanavir eller darunavir), som har begrænset, oral biotilgængelighed og en kort halveringstid på grund af den CYP3A-afhængige metabolisme. 
Inhibition of CYP3A-mediated metabolism by cobicistat enhances the systemic exposure of CYP3A substrates (such as atazanavir or darunavir) that have limited oral bioavailability and a short half-life due to CYP3A-dependent metabolism.
Øgede plasmakoncentrationer af lægemidler, der metaboliseres af CYP3A (inklusiv atazanavir og darunavir) ses ved samtidig administration af cobicistat. 
Increased plasma concentrations of medicinal products that are metabolised by CYP3A (including atazanavir and darunavir) are observed on co-administration with cobicistat.
Tabel 4: Farmakokinetiske parametre [middel ± SD (% CV)] af atazanavir i den farmakokinetiske undergruppe i fase 3 (studie GS-US-216-0114) 
Table 4: Pharmacokinetic parameters [mean ± SD (%CV)] of atazanavir in the pharmacokinetic sub-study of phase 3 Study GS-US-216-0114
Kortikosteroider, som er mindre afhængige af CYP3Ametabolisering, f.eks. nasal eller inhaleret beclomethason, bør overvejes, navnlig ved langvarig brug. 
Alternative corticosteroids which are less dependent on CYP3A metabolism e.g. beclomethasone for intranasal or inhalational use should be considered, particularly for long-term use.
hyperbilirubinæmi Hud og subkutane væv: Almindelig: 
hyperbilirubinaemia Skin and subcutaneous tissue disorders: Common:
Sikkerheden og virkningen af cobicistat med atazanavir hos hiv-1-inficerede patienter blev evalueret i et randomiseret, dobbeltblindet, aktivt-kontrolleret fase 3 studie GS-US-216-0114 hos hiv-1-inficerede patienter med baseline estimeret kreatininclearance over 70 ml/min, som var behandlingsnaive (n = 692). 
The safety and efficacy of cobicistat with atazanavir in HIV-1 infected patients were evaluated in the randomised, double-blind, active-controlled phase 3 Study GS-US-216-0114 in HIV-1 infected patients with baseline estimated creatinine clearance above 70 ml/min who were treatment-naïve (n = 692).
Tybosts sikkerhed hos 73 hiv-1-inficerede behandlingserfarne patienter med let til moderat nedsat nyrefunktion (eGFR 50-89 ml/min efter Cockcroft-Gault-metoden), som skiftede farmakokinetisk forstærker fra ritonavir til cobicistat, blev evalueret i et åbent klinisk studie (GS-US-236-0118) med cobicistat-boostet atazanavir eller darunavir plus to NRTI'er. 
The safety of Tybost in 73 HIV-1 infected treatment-experienced patients with mild to moderate renal impairment (eGFR by Cockcroft-Gault method 50-89 ml/min) who switched pharmacokinetic enhancer from ritonavir to cobicistat was evaluated in an open-label clinical Study (GS-US-236-0118) of cobicistat-boosted atazanavir or darunavir plus two NRTIs.
Koncentrationer af itraconazol, fluconazol og posaconazol kan øges ved samtidig administration af cobicistat. 
Concentrations of itraconazole, fluconazole and posaconazole may be increased when co-administered with cobicistat.
Clorazepat 
Clorazepate
Tybost anbefales derfor ikke til disse patienter (se pkt. 
Therefore, the use of Tybost is not recommended in these patients (see sections 4.4 and 5.2).
I studie GS-US-216-0114 var hyperbilirubinæmi (> 1 x ULN) almindelig: 97,7 % i cobicistat-boostet atazanavir plus emtricitabin og tenofovirdisoproxilfumarat i fastdosis-kombination-gruppen og 97,4 % i ritonavir-boostet atazanavir plus emtricitabin og tenofovirdisoproxilfumarat i fastdosis-kombinationgruppen til og med 144 ugers behandling. 
In Study GS-US-216-0114, hyperbilirubinaemia (> 1 x ULN) was common: 97.7% in the cobicistatboosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group, and 97.4% in the ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group through 144 weeks of treatment.
 Fortæl lægen, hvis De tager nogle af disse lægemidler. 
 Tell your doctor if you are taking any of these HIV medicines.
Darunavirs farmakokinetiske parametre 
Darunavir pharmacokinetics parameters
nephrolithiasis, hæmaturi, proteinuri Almene symptomer og reaktioner på administrationsstedet: Almindelig: 
nephrolithiasis, haematuria, proteinuria General disorders and administration site conditions: Common:
Cobicistats farmakokinetik hos pædiatriske personer er ikke klarlagt. 
The pharmacokinetics of cobicistat in paediatric subjects have not been established.
Ingen dosisjustering af cobicistat er nødvendig for patienter med let til moderat nedsat leverfunktion. 
No dose adjustment of cobicistat is necessary for patients with mild to moderate hepatic impairment.
For yderligere lægemiddelinteraktioner med atazanavir eller darunavir, konsulteres deres respektive produktresumé, når der anvendes Tybost. 
For additional drug-drug interactions with atazanavir or darunavir, consult their respective Summary of Product Characteristics when using Tybost.
Sikkerhed og virkning er ikke blevet klarlagt for anvendelse af cobicistat med enten atazanavir eller darunavir ved anvendelse i andre doseringsplaner. 
Safety and efficacy have not been established for use of cobicistat with either atazanavir or darunavir when used in any other dosing regimen.
Tybost bruges i kombination med atazanavir eller darunavir, og produktresuméet for atazanavir eller darunavir skal derfor konsulteres. 
Tybost is used in combination with atazanavir or darunavir, therefore the atazanavir or darunavir Summary of Product Characteristics should be consulted.
Behandling med cobicistat og darunavir under graviditet medfører lavere eksponering for darunavir. 
Treatment with cobicistat and darunavir during pregnancy results in lower darunavir exposure.
GLUKOKORTIKOIDER 
GLUCOCORTICOIDS
Plasmakoncentrationen af disse lægemidler kan øges ved samtidig administration af cobicistat, hvilket medfører nedsat serumkortisol. 
Plasma concentrations of these medicinal products may be increased when co-administered with cobicistat, resulting in reduced serum cortisol concentrations.
Tybost må ikke påbegyndes hos patienter med kreatininclearance under 70 ml/min, hvis en eller flere samtidigt indgivne stoffer kræver dosisjustering baseret på kreatininclearance (f.eks. emtricitabin, lamivudin, tenofovirdisoproxil eller adefovir). 
Tybost should not be initiated in patients with creatinine clearance less than 70 ml/min if one or more co-administered agent requires dose adjustment based on creatinine clearance (e.g. emtricitabine, lamivudine, tenofovir disoproxil or adefovir).
Den farmakokinetiske forstærkende virkning af cobicistat på darunavir blev evalueret i et fase 1 kliniskstudie GS-US-216-0115 med 31 sunde forsøgspersoner, der fik administreret darunavir 800 mg i kombination med cobicistat 150 mg eller ritonavir 100 mg, alle én gang dagligt, i 10 dage. 
The pharmacokinetic enhancing effect of cobicistat on darunavir was evaluated in a phase 1 clinical Study GS-US-216-0115 in 31 healthy subjects that were administered darunavir 800 mg in combination with cobicistat 150 mg or ritonavir 100 mg, all once daily, for 10 days.
Peak-koncentrationen af digoxin øges ved samtidig administration af Tybost. 
The peak concentration of digoxin is increased when co-administered with Tybost.
Tag altid den dosis, Deres læge har anbefalet for at sikre, at medicinen er fuldt ud effektiv. 
Always take the dose recommended by your doctor.
Samtidig administration af cobicistat kan føre til øgede plasmakoncentrationer af DOAK-præparatet, hvilket kan føre til en øget blødningsrisiko. 
Co-administration with cobicistat may result in increased plasma concentrations of the DOAC, which may lead to an increased bleeding risk..
[Kun på den ydre emballage] 
[Outer packaging only]
Sådan skal De tage Tybost 
How to take Tybost
(dyspepsi), oppustethed, afgang af tarmluft (flatulens) 
(dyspepsia), feeling bloated, wind (flatulence)
Samtidig administration med lægemidler, som er meget afhængige af CYP3A for clearance, og for hvilke forhøjede plasmakoncentrationer er associeret med alvorlige og/eller livstruende hændelser, er kontraindiceret. 
Co-administration is contraindicated with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
Sygdomskarakteristika ved baseline 
Baseline disease characteristics
Middelændringen (± SD) i estimeret glomerulær filtrationsrate (eGFR) efter Cockcroft-Gault-metoden efter 144 ugers behandling var -15,1 ± 16,5 ml/min i cobicistat-boostet atazanavir plus emtricitabin og tenofovirdisoproxilfumarat i fastdosis-kombination-gruppen og -8,0 ± 16,8ml/min i ritonavir-boostet atazanavir plus emtricitabin og tenofovirdisoproxilfumarat i fastdosis-kombination-gruppen. 
The mean (± SD) change in estimated glomerular filtration rate (eGFR) by Cockcroft-Gault method after 144 weeks of treatment was -15.1 ± 16.5 ml/min in the cobicistat-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group and -8.0 ± 16.8 ml/min in the ritonavir-boosted atazanavir plus emtricitabine and tenofovir disoproxil fumarate fixed-dose combination group.
Nukleosid-revers transkriptase-hæmmere (NRTI'er) Tenofovirdisoproxil1 
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Tenofovir disoproxil1
Samtidig brug af cobicistat og kortikosteroider, der metaboliseres via CYP3A (f.eks. fluticasonpropionat eller andre inhalerede eller nasale kortikosteroider) kan øge risikoen for systemiske kortikosteroid-bivirkninger, herunder Cushings syndrom og binyrebarksuppression. 
Concomitant use of cobicistat and corticosteroids that are metabolised by CYP3A (e.g. fluticasone propionate or other inhaled or nasal corticosteroids) may increase the risk of development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.
Ingen dosisjustering af rilpivirin er nødvendig, når atazanavir/cobicistat eller darunavir/cobicistat anvendes samtidig med rilpivirine. 
No dose adjustment of rilpivirine is required when atazanavir/cobicistat or darunavir/cobicistat are used concomitantly with rilpivirine.
Samtidig administration af Tybost kan føre til øgede plasmakoncentrationer af dabigatran med lignende virkninger som ved andre kraftige hæmmere af P-gp. 
Co-administration with Tybost may increase dabigatran plasma concentrations with similar effects as seen with other strong P-gp inhibitors.
Cobicistat er en kraftig mekanisme baseret CYP3A-hæmmer og et CYP3A-substrat. 
Cobicistat is a strong mechanism-based CYP3A inhibitor and is a CYP3A substrate.
I kliniske studier blev cobicistat administreret samtidig med atazanavir eller darunavir i forbindelse med måltider i henhold til produktresuméet for disse stoffer. 
In clinical studies, cobicistat was co-administered with atazanavir or darunavir under fed conditions, in accordance with the Summary of Product Characteristics for these agents.
Darunavir 800 mg + ritonavir 100 mg én gang dagligt (n = 31) 
Darunavir 800 mg + ritonavir 100 mg once daily (n = 31)
Tabel 5: Farmakokinetiske parametre [middel ± SD (% CV)] af darunavir 800 mg administreret samtidig med cobicistat 150 mg eller ritonavir 100 mg én gang dagligt 
Table 5: Pharmacokinetic parameters [mean ± SD (%CV)] of darunavir 800 mg co-administered with cobicistat 150 mg or ritonavir 100 mg once daily
Cobicistats sikkerhed er baseret på 144 ugers data fra et randomiseret, aktivt-kontrolleret klinisk fase 3-studie (GS-US-216-0114), i hvilket 692 behandlingsnaive patienter fik mindst én dosis cobicistatboostet atazanavir (n = 344) eller ritonavir-boostet atazanavir (n = 348) administreret med embricitabin og tenofovirdisoproxilfumarat i fastdosis-kombination. 
The safety of cobicistat is based on 144-week data from a phase 3, randomised, active-controlled clinical Study (GS-US-216-0114), in which 692 treatment-naïve patients received at least one dose of cobicistat-boosted atazanavir (n = 344) or ritonavir-boosted atazanavir (n = 348) administered with emtricitabine and tenofovir disoproxil fumarate fixed-dose combination.
Darunavirs steady-state farmakokinetiske parametre kunne sammenlignes, når de blev boostet med cobicistat versus ritonavir (se tabel 5). 
The steady-state pharmacokinetic parameters of darunavir were comparable when boosted with cobicistat versus ritonavir (see Table 5).
Behandling med cobicistat må ikke påbegyndes hos patienter med kreatininclearance under 70 ml/min, såfremt samtidigt administrerede stoffer (f.eks. emtricitabin, lamivudin, tenofovirdisproxil eller adefovir) kræver dosisjustering baseret på kreatininclearance. 
Cobicistat should not be initiated in patients with creatinine clearance less than 70 ml/min if any co-administered agent (e.g. emtricitabine, lamivudine, tenofovir disoproxil, or adefovir) requires dose adjustment based on creatinine clearance.
Alternative antibiotika bør overvejes ved samtidig administration af atazanavir/cobicistat. 
Alternative antibiotics should be considered for co-administration with atazanavir/cobicistat.
Hvis der skiftes farmakobooster fra ritonavir til cobicistat, skal der udvises forsigtighed i løbet af de første to ugers behandling med cobicistat, især hvis doser af samtidigt indgivne lægemidler er blevet titreret eller justeret under brugen af ritonavir som en farmakobooster (se pkt. 
If switching pharmacoenhancer from ritonavir to cobicistat, caution is required during the first two weeks of treatment with cobicistat, particularly if doses of any concomitantly administered medicinal products have been titrated or adjusted during use of ritonavir as a pharmacoenhancer (see section 4.5).
pyreksi, asteni 
pyrexia, asthenia
Baselinekarakteristika og behandlingsresultater ved uge 48 og 144 for studie GS-US-216-0114 er anført i hhv. tabel 6 og 7. 
Baseline characteristics and treatment outcomes at weeks 48 and 144 for Study GS-US-216-0114 are presented in Tables 6 and 7, respectively.
Der er ikke blevet identificeret klinisk relevante farmakokinetiske forskelle på grund af køn for cobicistat. 
No clinically relevant pharmacokinetic differences due to gender have been identified for cobicistat.
Pakningsstørrelser, der indeholder 1 tabletbeholder med 30 filmovertrukne tabletter eller 3 tabletbeholdere med 30 filmovertrukne tabletter. 
Pack sizes containing 1 bottle of 30 film-coated tablets or 3 bottles of 30 film-coated tablets.
Der er ikke blevet identificeret klinisk relevante farmakokinetiske forskelle på grund af etnicitet for cobicistat. 
No clinically relevant pharmacokinetic differences due to ethnicity have been identified for cobicistat.
c Omfatter personer som havde ≥ 50 kopier/ml i uge 48- eller 144-vinduet, personer som afbrød behandlingen tidligt som følge af manglende eller svigtende virkning, personer, som afbrød behandlingen af andre årsager end en adverse event, død eller manglende eller svigtende virkning, og som på tidspunktet for seponering havde en viral load på ≥ 50 kopier/ml. 
Missing data during window but on study drug a Week 48 window is between day 309 and 378 (inclusive) b Week 144 window is between day 967 and 1,050 (inclusive) c Includes subjects who had ≥ 50 copies/ml in the week 48 or 144 windows; subjects who discontinued early due to lack or loss of efficacy; subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy, and at the time of discontinuation had a viral value of ≥ 50 copies/ml.
Hvis der skiftes farmakobooster fra ritonavir til cobicistat, skal der udvises forsigtighed i løbet af de første to ugers behandling med Tybost, især hvis doser af nogle af de samtidigt indgivne lægemidler er blevet titreret eller justeret under brugen af ritonavir som en farmakobooster (se pkt. 
If switching pharmacoenhancer from ritonavir to cobicistat, caution is required during the first two weeks of treatment with Tybost, particularly if doses of any concomitantly administered medicinal products have been titrated or adjusted during use of ritonavir as a pharmacoenhancer (see section 4.4).
• en anden proteasehæmmer 
• another protease inhibitor
Samtidig infektion med hepatitis B- og/eller hepatitis C-virus Cobicistats farmakokinetik er ikke blevet fuldt evalueret hos forsøgspersoner med samtidig infektion med hepatitis B- og/eller hepatitis C-virus. 
Pharmacokinetics of cobicistat have not been fully evaluated in hepatitis B and/or C virus co-infected subjects.
Selektive serotoningenoptagelseshæmmere (SSRI'er) Trazodon 
Selective Serotonin Reuptake Inhibitors (SSRIs) Trazodone
AUCtau (µg•t/ml) Cmax (µg/ml) Ctau (µg/ml) a Plus baggrundsbehandlingsplan med emtricitabin 200 mg og tenofovirdisoproxilfumarat 300 mg i fastdosis-kombination 
AUCtau (µg•h/ml) Cmax (µg/ml) Ctau (µg/ml) a Plus background regimen of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg fixed-dose combination
Plasmakoncentrationerne af atazanavir eller darunavir kan falde som følge af en reduktion i plasmakoncentrationerne af cobicistat, hvilket kan forårsage svigtende terapeutisk virkning og udvikling af resistens. 
Atazanavir or darunavir plasma concentrations may decrease as a consequence of a reduction in cobicistat plasma concentrations, which may result in loss of therapeutic effect and development of resistance.
Et farmakokinetikstudie af cobicistat blev udført hos non-hiv-1-inficerede personer med moderat nedsat leverfunktion (Child-Pugh klasse B). 
A study of the pharmacokinetics of cobicistat was performed in non-HIV-1 infected subjects with moderate hepatic impairment (Child-Pugh Class B).
Atazanavirs steady-state farmakokinetiske parametre kunne sammenlignes, når de blev boostet med cobicistat versus ritonavir (se tabel 4). 
The steady-state pharmacokinetic parameters of atazanavir were comparable when boosted with cobicistat versus ritonavir (see Table 4).
Der blev ikke observeret nogen betydningsfulde forskelle i farmakokinetikken for cobicistat hos personer med svært nedsat nyrefunktion og hos raske personer, hvilket er i overensstemmelse med corbicistats lave nyreclearance. 
No meaningful differences in cobicistat pharmacokinetics were observed between subjects with severe renal impairment and healthy subjects, consistent with low renal clearance of cobicistat.
Ingen forsøgsperson udviklede de tenofovirassocierede resistenssubstitutioner K65R eller K70E, eller nogen primær resistenssubstitution associeret med proteasehæmmere. 
K65R or K70E, or any primary resistance substitution associated with protease inhibitors.
Indlægsseddel: Information til patienten Tybost 150 mg filmovertrukne tabletter cobicistat 
Package leaflet: Information for the patient Tybost 150 mg film-coated tablets cobicistat
Aktivt stof: cobicistat. 
The active substance is cobicistat.
Virkningen af cobicistat på atazanavir farmakokinetik blev påvist i den farmakokinetiske undergruppe (n = 48) i fase 3-studiet GS-US-216-0114 i hvilket hiv-1-inficerede patienter fik atazanavir 300 mg + cobicistat 150 mg eller atazanavir 300 mg + ritonavir 100 mg, begge i kombination med emtricitabin og tenofovirdisoproxilfumarat i fastdosis-kombination. 
The effect of cobicistat on atazanavir pharmacokinetics was demonstrated in the pharmacokinetic substudy (n = 48) of the phase 3 Study GS-US-216-0114 in which HIV-1 infected patients received atazanavir 300 mg + cobicistat 150 mg or atazanavir 300 mg + ritonavir 100 mg, both in combination with emtricitabine and tenofovir disoproxil fumarate fixed-dose combination.
Tabel 8: Ændringer i CD4+ celletal til og med uge 48 og 144 i studie GS-US-216-0114 Uge 48 
Table 8: Changes in CD4+ cell counts through weeks 48 and 144 in Study GS-US-216-0114 Week 48
Dosisjustering af cobicistat er ikke nødvendigt hos patienter med let nedsat (Child-Pugh klasse A) eller moderat nedsat (Child-Pugh klasse B) leverfunktion. 
No dose adjustment of cobicistat is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment (Child-Pugh Class B).
Alternative eller yderligere forholdsregler vedrørende kontraception anbefales, når østrogenbaserede antikonceptiva administreres samtidig med darunavir/cobicistat. 
Alternative or additional contraceptive measures are recommended when oestrogen-based contraceptives are co-administered with darunavir/cobicistat.
Samtidig administration med cobicistat kan føre til øgede plasmakoncentrationer af sildenafil, tadalafil og vardenafil, hvilket kan føre til bivirkninger associeret med PDE-5-hæmmeren. 
Co-administration with cobicistat may result in increased sildenafil, tadalafil and vardenafil plasma concentrations, which may result in PDE-5 inhibitorassociated adverse reactions.
Tabel 3: Oversigt over bivirkninger af cobicistat-boostet atazanavir baseret på 144 ugers observation i fase 3-studiet GS-US-216-0114 
Table 3: Tabulated summary of adverse reactions to cobicistat-boosted atazanavir based on experience of 144 weeks from phase 3 Study GS-US-216-0114
Digoxin (0,5 mg enkeltdosis)/Cobicistat (150 mg flerdosis) 
Digoxin (0.5 mg single dose)/Cobicistat (150 mg multiple doses)
• naturlægemiddel: prikbladet perikum (Hypericum perforatum) 
• herbal products: St. John's wort (Hypericum perforatum)
Koncentrationer af ketoconazol og/eller cobicistat kan øges ved samtidig administration af cobicistat. 
Concentrations of ketoconazole and/or cobicistat may increase with co-administration of cobicistat.
Klinisk overvågning anbefales og en dosisreduktion kan være nødvendig ved samtidig administration af betablokkere og Tybost. 
Clinical monitoring is recommended and a dose reduction may be necessary when these beta-blockers are co-administered with Tybost.
Der blev ikke observeret nogen klinisk relevante forskelle i farmakokinetikken for cobicistat hos personer med moderat nedsat leverfunktion og hos raske personer. 
No clinically relevant differences in cobicistat pharmacokinetics were observed between subjects with moderate impairment and healthy subjects.