natgillin/translations-raw huggingface dataset:
rifabutin AUC ↓ 0, 83 (0, 75- 0, 94) rifabutin Cmin ↓ 0, 76 (0, 66- 0, 87) rifabutin Cmax ↓ 0, 90 (0, 78- 1, 03) 25- O- desacetylrifabutin AUC ↓ 0, 83 (0, 74- 0, 92) 25- O- desacetylrifabutin Cmin ↓ 0, 78 (0, 70- 0, 87) 25- O- desacetylrifabutin Cmax ↓ 0, 85 (0, 72- 1, 00) etravirin AUC ↓ 0, 63 (0, 54- 0, 74) etravirin Cmin ↓ 0, 65 (0, 56- 0, 74) etravirin Cmax ↓ 0, 63 (0, 53- 0, 74)
rifabutin AUC ↓ 0.83 (0.75-0.94) rifabutin Cmin ↓ 0.76 (0.66-0.87) rifabutin Cmax ↓ 0.90 (0.78-1.03) 25-O-desacetyl-rifabutin AUC ↓ 0.83 (0.74-0.92) 25-O-desacetyl-rifabutin Cmin ↓ 0.78 (0.70-0.87) 25-O-desacetyl-rifabutin Cmax ↓ 0.85 (0.72-1.00) etravirine AUC ↓ 0.63 (0.54-0.74) etravirine Cmin ↓ 0.65 (0.56-0.74) etravirine Cmax ↓ 0.63 (0.53-0.74)
Kombinationen af INTELENCE og rifabutin bør anvendes med forsigtighed på grund af risikoen for reduktion af etravirin - og rifabutineksponering.
The combination of INTELENCE and rifabutin should be used with caution due to the risk of decrease in etravirine and rifabutin exposures.
ANTIVIRALE MIDLER
ANTIVIRALS
Ikke undersøgt, men der forventes ingen interaktion, eftersom ribavirin elimineres via nyrerne.
Not studied, but no interaction expected based on the renal elimination pathway of ribavirin.
INTELENCE og ribavirin kan anvendes uden dosisjustering.
The combination of INTELENCE and ribavirin can be used without dose adjustments.
Etravirin forventes at øge plasmakoncentrationen af diazepam.
Not studied, etravirine is expected to increase plasma concentrations of diazepam.
ØSTROGENBASEREDE ANTIKONCEPTIVA
ESTROGEN-BASED CONTRACEPTIVES
Ethinyløstradiol 0, 035 mg q. d.
Ethinylestradiol 0.035 mg q. d.
Norethindron 1 mg q. d.
Norethindrone 1 mg q. d.
ethinyløstradiol AUC ↑ 1, 22 (1, 13- 1, 31) ethinyløstradiol Cmin ↔ 1, 09 (1, 01- 1, 18) ethinyløstradiol Cmax ↑ 1, 33 (1, 21- 1, 46) norethindron AUC ↔ 0, 95 (0, 90- 0, 99) norethindron Cmin ↓ 0, 78 (0, 68- 0, 90) norethindron Cmax ↔ 1, 05 (0, 98- 1, 12) etravirin AUC ↔a etravirin Cmin ↔a etravirin Cmax ↔a
ethinylestradiol AUC ↑ 1.22 (1.13-1.31) ethinylestradiol Cmin ↔ 1.09 (1.01-1.18) ethinylestradiol Cmax ↑ 1.33 (1.21-1.46) norethindrone AUC ↔ 0.95 (0.90-0.99) norethindrone Cmin ↓ 0.78 (0.68-0.90) norethindrone Cmax ↔ 1.05 (0.98-1.12) etravirine AUC ↔ a etravirine Cmin ↔ a etravirine Cmax ↔ a
Østrogen - og/ eller progesteronbaserede antikonceptiva og INTELENCE kan gives i kombination uden dosisjustering.
The combination of estrogen- and/ or progesterone-based contraceptives and INTELENCE can be used without dose adjustment.
Perikon forventes at reducere plasmakoncentrationen af etravirin.
St John’ s wort is expected to decrease the plasma concentrations of etravirine.
HMG- COA- REDUKTASEHÆMMERE
HMG CO-A REDUCTASE INHIBITORS
atorvastatin AUC ↓ 0, 63 (0, 58- 0, 68) atorvastatin Cmin ND atorvastatin Cmax ↓ 1, 04 (0, 84- 1, 30) 2- OH- atorvastatin AUC ↑ 1, 27 (1, 19- 1, 36) 2- OH- atorvastatin Cmin ND 2- OH- atorvastatin Cmax ↑ 1, 76 (1, 60- 1, 94) etravirin AUC ↔ 1, 02 (0, 97- 1, 07) etravirin Cmin ↔ 1, 10 (1, 02- 1, 19) etravirin Cmax ↔ 0, 97 (0, 93- 1, 02)
atorvastatin AUC ↓ 0.63 (0.58-0.68) atorvastatin Cmin ND atorvastatin Cmax ↓ 1.04 (0.84-1.30) 2-OH-atorvastatin AUC ↑ 1.27 (1.19-1.36) 2-OH-atorvastatin Cmin ND 2-OH-atorvastatin Cmax ↑ 1.76 (1.60-1.94) etravirine AUC ↔ 1.02 (0.97-1.07) etravirine Cmin ↔ 1.10 (1.02-1.19) etravirine Cmax ↔ 0.97 (0.93-1.02)
Der forventes ingen interaktion mellem pravastatin og INTELENCE.
No interaction between pravastatin and INTELENCE is expected.
Lovastatin, rosuvastatin og simvastatin er CYP3A4- substrater, og samtidig indgift med INTELENCE kan reducere plasmakoncentrationen af HMG- CoA - reduktasehæmmeren.
Lovastatin, rosuvastatin and simvastatin are CYP3A4 substrates and co-administration with INTELENCE may result in lower plasma concentrations of the HMG Co-A reductase inhibitor.
Fluvastatin og rosuvastatin metaboliseres af CYP2C9, og samtidig indgift af INTELENCE kan øge plasmakoncentrationen af HMG- CoA- reduktasehæmmeren.
Fluvastatin, and rosuvastatin are metabolised by CYP2C9 and co-administration with INTELENCE may result in higher plasma concentrations of the HMG Co-A reductase inhibitor.
Det kan være nødvendigt at justere dosis af disse HMG - CoA- reduktasehæmmere.
Dose adjustments for these HMG Co-A reductase inhibitors may be necessary.
H2- RECEPTORANTAGONISTER
H2-RECEPTOR ANTAGONISTS
etravirin AUC ↓ 0, 86 (0, 76- 0, 97) etravirin Cmin ND etravirin Cmax ↓ 0, 94 (0, 75- 1, 17)
etravirine AUC ↓ 0.86 (0.76-0.97) etravirine Cmin ND etravirine Cmax ↓ 0.94 (0.75-1.17)
INTELENCE kan indgives sammen med H2- receptorantagonister uden dosisjustering.
INTELENCE can be co-administered with H2-receptor antagonists without dose adjustments.
Ciclosporin Sirolimus Tacrolimus
Cyclosporine Sirolimus Tacrolimus
Etravirin forventes at reducere plasmakoncentrationen af ciclosporin, sirolimus og tacrolimus.
Etravirine is expected to decrease plasma concentrations of cyclosporine, sirolimus or tacrolimus.
Forsigtighed tilrådes ved samtidig indgift med systemiske immunsuppressiva, fordi plasmakoncentrationen af ciclosporin, sirolimus og tacrolimus kan blive påvirket ved indgift sammen med INTELENCE.
Co-administration with systemic immunosuppressants should be done with caution because plasma concentrations of cyclosporine, sirolimus or tacrolimus may be affected when co-administered with INTELENCE.
Metadon individuel dosering 60- 130 mg q. d.
Methadone individual dose ranging from 60 mg to 130 mg q. d.
R (-) metadon AUC ↔ 1, 06 (0, 99- 1, 13) R (-) metadon Cmin ↔ 1, 10 (1, 02- 1, 19) R (-) metadon Cmax ↔ 1, 02 (0, 96- 1, 09) S( +) metadon AUC ↔ 0, 89 (0, 82- 0, 96) S( +) metadon Cmin ↔ 0, 89 (0, 81- 0, 98) S( +) metadon Cmax ↔ 0, 89 (0, 83- 0, 97) etravirin AUC ↔a etravirin Cmin ↔a etravirin Cmax ↔a
R(-) methadone AUC ↔ 1.06 (0.99-1.13) R(-) methadone Cmin ↔ 1.10 (1.02-1.19) R(-) methadone Cmax ↔ 1.02 (0.96-1.09) S(+) methadone AUC ↔ 0.89 (0.82-0.96) S(+) methadone Cmin ↔ 0.89 (0.81-0.98) S(+) methadone Cmax ↔ 0.89 (0.83-0.97) etravirine AUC ↔ a etravirine Cmin ↔ a etravirine Cmax ↔ a
FOSFODIESTERASE- 5- HÆMMERE (PDE5- HÆMMERE)
PHOSPHODIESTERASE, TYPE 5 (PDE-5) INHIBITORS
Sildenafil 50 mg enkeltdosis Vardenafil Tadalafil
Sildenafil 50 mg single dose Vardenafil Tadalafil
sildenafil AUC ↓ 0, 43 (0, 36- 0, 51) sildenafil Cmin ND sildenafil Cmax ↓ 0, 55 (0, 40- 0, 75) N- desmetylsildenafil AUC ↓ 0, 59 (0, 52- 0, 68) N- desmetylsildenafil Cmin ND N- desmetylsildenafil Cmax ↓ 0, 75 (0, 59- 0, 96)
sildenafil AUC ↓ 0.43 (0.36-0.51) sildenafil Cmin ND sildenafil Cmax ↓ 0.55 (0.40-0.75) N-desmethyl-sildenafil AUC ↓ 0.59 (0.52-0.68) N-desmethyl-sildenafil Cmin ND N-desmethyl-sildenafil Cmax ↓ 0.75 (0.59-0.96)
Ved samtidig brug af PDE5- hæmmere og INTELENCE kan det være nødvendigt at justere dosis af PDE5- hæmmeren for at opnå den ønskede kliniske effekt.
Concomitant use of PDE-5 inhibitors with INTELENCE may require dose adjustment of the PDE-5 inhibitor to attain the desired clinical effect.
etravirin AUC ↑ 1, 41 (1, 22- 1, 62) etravirin Cmin ND etravirin Cmax ↑ 1, 17 (0, 96- 1, 43)
etravirine AUC ↑ 1.41 (1.22-1.62) etravirine Cmin ND etravirine Cmax ↑ 1.17 (0.96-1.43)
paroxetin AUC ↔ 1, 03 (0, 90- 1, 18) paroxetin Cmin ↓ 0, 87 (0, 75- 1, 02) paroxetin Cmax ↔ 1, 06 (0, 95- 1, 20) etravirin AUC ↔ 1, 01 (0, 93- 1, 10) etravirin Cmin ↔ 1, 07 (0, 98- 1, 17) etravirin Cmax ↔ 1, 05 (0, 96- 1, 15)
paroxetine AUC ↔ 1.03 (0.90-1.18) paroxetine Cmin ↓ 0.87 (0.75-1.02) paroxetine Cmax ↔ 1.06 (0.95-1.20) etravirine AUC ↔ 1.01 (0.93-1.10) etravirine Cmin ↔ 1.07 (0.98-1.17) etravirine Cmax ↔ 1.05 (0.96-1.15)
I lægemiddelinteraktionsforsøg blev der anvendt forskellige formuleringer og/ eller doser af etravirin, som førte til nogenlunde ens eksponeringer, og interaktioner, som er relevante for den ene formulering, er derfor også relevante for den anden.
In drug-drug interaction studies, different formulations and/ or doses of etravirine were used which led to similar exposures and, therefore, interactions relevant for one formulation are relevant for the other.
Graviditet Der er ikke udført tilstrækkelige og velkontrollerede forsøg med etravirin til gravide kvinder.
Pregnancy There are no adequate and well-controlled studies with etravirine in pregnant women.
Placental overførsel er set hos drægtige rotter, men det vides ikke, om placental overførsel af INTELENCE også finder sted hos gravide kvinder.
Placental transfer has been seen in pregnant rats, but it is not known whether placental transfer of INTELENCE also occurs in pregnant women.
5. 3).
Studies in animals do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development (see section 5.3).
INTELENCE bør kun anvendes under graviditet, hvis de forventede fordele opvejer den potentielle risiko.
INTELENCE should be used during pregnancy only if the potential benefit justifies the potential risk.
Amning Det vides ikke, om etravirin udskilles i human brystmælk.
Breastfeeding It is not known whether etravirine is excreted in human milk.
På grund af både den potentielle risiko for HIV- smitte og risikoen for bivirkninger hos det ammede barn bør kvinder informeres om, at de ikke bør amme, hvis de er i behandling med INTELENCE.
Because of both the potential for HIV transmission and the potential for adverse reactions in breast-fed infants, mothers should be instructed not to breast-feed if they are receiving INTELENCE.
Fertilitet Der findes ingen data om etravirins virkning på fertiliteten hos mennesker.
Fertility No human data on the effect of etravirine on fertility are available.
5. 3).
In rats, there was no effect on mating or fertility with etravirine treatment (see section 5.3).
Der er ikke foretaget undersøgelser af virkningen af INTELENCE på evnen til at føre motorkøretøj eller betjene maskiner.
No studies on the effects of INTELENCE on the ability to drive or operate machines have been performed.
4. 8) er bivirkninger såsom somnolens og vertigo rapporteret med en hyppighed sammenlignelig med placebo.
Adverse drug reactions such as somnolence and vertigo have been reported in INTELENCE treated subjects at incidences similar to placebo (see section 4.8).
Der findes ingen evidens for, at INTELENCE skulle ændre patienternes evne til at føre motorkøretøj eller betjene maskiner, men bivirkningsprofilen bør dog tages i betragtning.
There is no evidence that INTELENCE may alter the patient’ s ability to drive and operate machines, however, the adverse drug reaction profile should be taken into account.
5. 1).
The safety assessment is based on all data from 1,203 patients in the ongoing Phase III placebo-controlled trials DUET-1 and DUET-2 in antiretroviral treatment-experienced HIV-1 infected adult patients, 599 of whom received INTELENCE (200 mg b. i. d.) (see section 5.1).
I disse poolede forsøg var medianeksponeringen for patienterne i INTELENCE- gruppen 30 uger.
In these pooled trials, the median exposure for patients in the INTELENCE arm was 30 weeks.
De hyppigst rapporterede bivirkninger (incidens ≥ 10% i INTELENCE- gruppen) uanset sværhedsgrad, der forekom i fase III- forsøgene, var udslæt (17, 0% i INTELENCE- gruppen versus 9, 4% i placebogruppen), diaré (15, 0% versus 20, 4%) og kvalme (13, 9% versus 11, 1%).
The most frequently reported adverse drug reactions (ADRs) (incidence ≥ 10% in the INTELENCE arm) of all intensities occurring in the Phase III studies were rash (17.0% in the INTELENCE arm versus 9.4% in the placebo arm), diarrhoea (15.0% versus 20.4%) and nausea (13.9% versus 11.1%).
Behandlingsophør på grund af bivirkninger forekom hos 5, 8% af de patienter, som fik INTELENCE, og hos 4, 5% af de patienter, som fik placebo.
The rates of discontinuation due to any adverse reaction were 5.8% in patients receiving INTELENCE and 4.5% in patients receiving placebo.
Den mest almindelige bivirkning, som førte til ophør, var udslæt (2, 0% i INTELENCE- gruppen versus 0% i placebogruppen).
The most common ADR leading to discontinuation was rash (2.0% in the INTELENCE arm versus 0% in the placebo arm).
4. 4).
Rash was mostly self-limiting, and generally resolved within 1-2 weeks on continued therapy (see section 4.4).
Incidensen af udslættet var højere blandt kvinder end blandt mænd i INTELENCE- gruppen.
The incidence of rash was higher in women compared to men in the INTELENCE arm.
Der var ingen forskel mellem kønnene med hensyn til sværhedsgrad eller behandlingsophør på grund af udslæt.
The clinical data are limited and
4. 4).
10 an increased risk of cutaneous reactions in patients with a history of NNRTI-associated cutaneous reaction cannot be excluded (see section 4.4).
Bivirkninger af moderat intensitet eller værre (≥ grad 2), som blev rapporteret hos patienter i behandling med INTELENCE, opsummeres i tabellen nedenfor (baggrundsregime angives som "BR").
ADRs of moderate intensity or greater (≥ grade 2) reported in patients treated with INTELENCE are summarised in the table below (background regimen is indicated as “ BR”).
Laboratorieanormaliteter, der betragtes som bivirkninger, er anført i et afsnit under tabellen.
Laboratory abnormalities considered ADRs are included in a paragraph below the table.
Frekvenserne defineres som meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 til < 1/ 10) og ikke almindelig (≥ 1/ 1. 000 til < 1/ 100).
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10) and uncommon (≥ 1/ 1,000 to < 1/ 100).
Baseret på antallet af patienter inkluderet i DUET- forsøgene kan sjældne og meget sjældne bivirkninger ikke påvises.
Rare and very rare ADRs cannot be detected based on the number of patients included in the DUET trials.
Forsøg DUET- 1 og DUET- 2 Systemorganklasse
DUET-1 and DUET-2 trials System Organ Class (SOC)
Frekvens - kategori
Frequency Category
myokardieinfarkt (0, 5% over for 0, 2%), atrieflimmer (0, 2% over for 0%), angina pectoris (0, 3% over for 0, 2%)
myocardial infarction (0.5% vs 0.2%), atrial fibrillation (0.2% vs 0%), angina pectoris (0.3% vs 0.2%)
trombocytopeni (1, 3% over for 1, 3%), anæmi (3, 5% over for 3, 6%)
thrombocytopaenia (1.3% vs 1.3%), anaemia (3.5% vs 3.6%)
almindelig
common uncommon
perifer neuropati (2, 8% over for 1, 8%), hovedpine (2, 7% over for 4, 1%)
peripheral neuropathy (2.8% vs 1.8%), headache (2.7% vs 4.1%) convulsion (0.3% vs 0.5%), syncope (0.3% vs 0.3%), amnesia (0.2% vs 0.2%), tremor (0.2% vs 0.3%), somnolence (0.7% vs 0.5%), paraesthesia (0.7% vs 0.7%), hypoaesthesia (0.3% vs 0.2%), hypersomnia (0.2% vs 0%)
ikke almindelig
uncommon uncommon
konvulsion (0, 3% over for 0, 5%), synkope (0, 3% over for 0, 3%), amnesi (0, 2% over for 0, 2%), tremor (0, 2% over for 0, 3%), somnolens (0, 7% over for 0, 5%), paræstesi (0, 7% over for 0, 7%), hypæstesi (0, 3% over for 0, 2%), hypersomni (0, 2% over for 0%)
blurred vision (0.7% vs 0%) vertigo (0.2% vs 0.5%)
Øjne
Respiratory, thoracic and mediastinal disorders
sløret syn (0, 7% over for 0%)
bronchospasm (0.2% vs 0%), exertional dyspnoea (0.5% vs 0.5%)
vertigo (0, 2% over for 0, 5%)
Renal and urinary disorders
Luftveje, thorax og mediastinum Mave- tarm- kanalen
common
ikke almindelig almindelig
renal failure (1.5% vs 1.5%)
bronkospasme (0, 2% over for 0%), anstrengelsesdyspnø (0, 5% over for 0, 5%) gastroøsofageal refluks (1, 5% over for 1, 0%), diaré (5, 2% over for 9, 6%), opkastning (2, 3% over for 2, 0%), kvalme (4, 7% over for 3, 5%), abdominalsmerter (3, 0% over for 2, 5%), flatulens (1, 0% over for 1, 0%), gastritis (1, 0% over for 0, 7%)
Skin and subcutaneous tissue disorders
ikke almindelig
common uncommon
pankreatitis (0, 7% over for 0, 2%), hæmatemese (0, 2% over for 0%), stomatitis (0, 2% over for 0, 2%), konstipation (0, 3% over for 0, 5%), abdominal distension (0, 7% over for 1, 0%), mundtørhed (0, 2% over for 0%), kraftig opkastning (0, 2% over for 0%)
rash (9.0% vs 3.2%) swelling face (0.2% vs 0%), lipohypertrophy (0.3% vs 0.3%), night sweats (0.8% vs 0.8%), hyperhidrosis (0.5% vs 0.2%), prurigo (0.5% vs 0.5%), dry skin (0.3% vs 0.2%)
Nyrer og urinveje Hud og subkutane væv
Metabolism and nutrition disorders
almindelig almindelig ikke almindelig
common
nyresvigt (1, 5% over for 1, 5%) udslæt (9, 0% over for 3, 2%) hævelse i ansigtet (0, 2% over for 0%), lipohypertrofi (0, 3% over for 0, 3%), nattesved (0, 8% over for 0, 8%), hyperhidrose (0, 5% over for 0, 2%), prurigo (0, 5% over for 0, 5%), tør hud (0, 3% over for 0, 2%)
diabetes mellitus (1.0% vs 0.2%), hyperglycaemia (1.2% vs 0.5%), hypercholesterolaemia (3.5% vs 2.2%), hypertriglyceridaemia (4.7% vs 3.0%), hyperlipidaemia (1.5% vs 0.7%), dyslipidaemia (1.0% vs 0.3%)
Metabolisme og ernæring
anorexia (0.7% vs 0.8%)
almindelig
common common uncommon
diabetes mellitus (1, 0% over for 0, 2%), hyperglykæmi (1, 2% over for 0, 5%), hyperkolesterolæmi (3, 5% over for 2, 2%), hypertriglyceridæmi (4, 7% over for 3, 0%), hyperlipidæmi (1, 5% over for 0, 7%), dyslipidæmi (1, 0% over for 0, 3%)
hypertension (2.8% vs 2.2%) fatigue (3.3% vs 4.0%) sluggishness (0.2% vs 0%)
anoreksi (0, 7% over for 0, 8%)
immune reconstitution syndrome (0.2% vs 0.2%), drug hypersensitivity (0.7% vs 0.7%)
hepatitis (0, 2% over for 0, 3%), steatosis hepatis (0, 2% over for 0%), cytolytisk hepatitis (0, 3% over for 0%), hepatomegali (0, 2% over for 0, 2%)
hepatitis (0.2% vs 0.3%), hepatic steatosis (0.2% vs 0%), cytolytic hepatitis (0.3% vs 0%), hepatomegaly (0.2% vs 0.2%)
gynækomasti (0, 2% over for 0%)
gynaecomastia (0.2% vs 0%)
konfusionstilstand (0, 2% over for 0, 2%), desorientering (0, 2% over for 0, 3%), mareridt (0, 2% over for 0, 2%), søvnforstyrrelser (0, 5% over for 0, 3%), nervøsitet (0, 2% over for 0, 2%), unormale drømme (0, 2% over for 0, 2%)
anxiety (1.2% vs 1.7%), insomnia (1.8% vs 2.2%) confusional state (0.2% vs 0.2%), disorientation (0.2% vs 0.3%), nightmares (0.2% vs 0.2%), sleep disorders (0.5% vs 0.3%), nervousness (0.2% vs 0.2%), abnormal dreams (0.2% vs 0.2%)
Yderligere bivirkninger af mindst moderat intensitet, som blev observeret i andre forsøg, var erhvervet lipodystrofi, angioneurotisk ødem, erythema multiforme og hæmorrhagia cerebri hver blev rapporteret hos højst 0, 5% af patienterne.
Additional ADRs of at least moderate intensity observed in other trials were acquired lipodystrophy, angioneurotic oedema, erythema multiforme and haemorrhagic stroke, each reported in no more than 0.5% of patients.
Stevens- Johnsons- syndrom blev rapporteret i sjældne tilfælde (< 0, 1%) under den kliniske udvikling af INTELENCE.
Stevens-Johnson Syndrome has been reported rarely (< 0.1%) during clinical development with INTELENCE.
Laboratorieabnormiteter Laboratoriemæssige abnomiteter, som krævede behandling (grad 3 eller 4), som blev betragtet som bivirkninger, og som blev rapporteret hos ≥ 2% af patienterne i henholdsvis INTELENCE- gruppen og placebogruppen, var: forhøjelse af amylase (7, 5% over for 7, 9%), lipase (2, 7% over for 1, 7%), totalkolesterol (5, 8% over for 4, 1%), lavdensitetslipoprotein (LDL) (5, 2% over for 5, 4%), triglycerider (7, 0% over for 4, 3%), glukose (2, 5% over for 2, 0%), alaninaminotransferase (ALAT) (2, 5% over for 1, 7%), aspartataminotransferase (ASAT) (2, 5% over for 1, 7%) og reduktion i neutrofilocytter (3, 7% over for 6, 3%).
Laboratory abnormalities Treatment emergent clinical laboratory abnormalities (grade 3 or 4), considered ADRs, reported in ≥ 2% of patients in the INTELENCE arm versus the placebo arm, respectively, were increases in amylase (7.5% vs 7.9%), lipase (2.7% vs 1.7%), total cholesterol (5.8% vs 4.1%), low density lipoprotein (LDL) (5.2% vs 5.4%), triglycerides (7.0% vs 4.3%), glucose (2.5% vs 2.0%), alanine aminotransferase (ALT) (2.5% vs 1.7%), aspartate amino transferase (AST) (2.5% vs 1.7%) and decreases in neutrophils (3.7% vs 6.3%).
4. 4).
Lipodystrophy Combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV infected patients, including loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump) (see section 4.4).
4. 4).
Immune reconstitution syndrome In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (immune reconstitution syndrome) (see section 4.4).
Osteonekrose Der er rapporteret tilfælde af osteonekrose, især hos patienter med generelt anerkendte risikofaktorer, fremskredet HIV- sygdom eller langvarig eksponering for antiretroviral kombinationsterapi.
Osteonecrosis Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy.
Yderligere oplysninger om særlige populationer Patienter, som samtidig er inficeret med hepatitis B - og/ eller hepatitis C- virus I den poolede analyse i forbindelse med DUET- 1 og DUET- 2 tenderede incidensen af leverpåvirkning være højere hos coinficerede patienter, som blev behandlet med INTELENCE, end hos coinficerede patienter i placebogruppen.
Additional information on special populations Patients co-infected with hepatitis B and/ or hepatitis C virus In the pooled analysis for DUET-1 and DUET-2, the incidence of hepatic events tended to be higher in co-infected subjects treated with INTELENCE compared to co-infected subjects in the placebo group.
4. 4 og 5. 2).
4.9 Overdose
12 4. 9 Overdosering
12 5.
NNRTI (non- nukleosid revers transkriptasehæmmer), ATC- kode: endnu ikke tildelt.
NNRTI (non-nucleoside reverse transcriptase inhibitor), ATC code: not yet assigned.
Virkningsmekanisme Etravirin er en NNRTI af humant immundefektvirus type 1 (HIV- 1).
Mechanism of action Etravirine is an NNRTI of human immunodeficiency virus type 1 (HIV-1).
Etravirin binder direkte til revers transkriptase (RT) og blokerer de RNA - og DNA- afhængige DNA- polymeraseaktiviteter ved at forstyrre enzymets katalytiske center.
Etravirine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site.
Antiviral in vitro- aktivitet Etravirin udviser aktivitet mod vild- type HIV- 1 i T- cellelinjer og primære celler med mediane EC50- værdier på 0, 9- 5, 5 nM.
Antiviral activity in vitro Etravirine exhibits activity against wild type HIV-1 in T-cell lines and primary cells with median EC50 values ranging from 0.9 to 5.5 nM.
Etravirin udviser aktivitet mod HIV- 1 gruppe M (undertype A, B, C, D, E, F og G) og HIV- 1 gruppe O primære isolater med EC50- værdier på henholdsvis 0, 3- 1, 7 nM og 11, 5- 21, 7 nM.
Etravirine demonstrates activity against HIV-1 group M (subtypes A, B, C, D, E, F, and G) and HIV-1 group O primary isolates with EC50 values ranging from 0.3 to 1.7 nM and from 11.5 to 21.7 nM, respectively.
Selvom etravirin udviser in vitro- aktivitet mod vild- type HIV- 2 med mediane EC50 - værdier på 5, 7- 7, 2 µM, anbefales det ikke at behandle HIV- 2- infektion med etravirin i mangel af kliniske data.
Although etravirine demonstrates in vitro activity against wild type HIV-2 with median EC50 values ranging from 5.7 to 7.2 µM, treatment of HIV-2 infection with etravirine is not recommended in the absence of clinical data.
Etravirin fastholder aktiviteten mod HIV- 1- virusstammer, som er resistente over for nukleosid revers transkriptase - og/ eller proteasehæmmere.
Etravirine retains activity against HIV-1 viral strains resistant to nucleoside reverse transcriptase and/ or protease inhibitors.
Endvidere udviser etravirin en fold- ændring (FC) i EC50- værdier ≤ 3 mod 60% af 6. 171 NNRTI- resistente kliniske isolater.
In addition, etravirine demonstrates a fold change (FC) in EC50 ≤ 3 against 60% of 6,171 NNRTI-resistant clinical isolates.
Resistens Effekten af etravirin i relation til NNRTI- resistens ved baseline er hovedsagelig blevet analyseret ved etravirin i kombination med darunavir/ ritonavir (DUET- 1 og - 2).
Resistance Etravirine efficacy in relation to NNRTI resistance at baseline has mainly been analysed with etravirine given in combination with darunavir/ ritonavir (DUET-1 and -2).