natgillin/translations-raw huggingface dataset:
I forbindelse med studier af patienter, som fik behandling med PI’ er, observeredes følgende mutationer hos de patienter, der fik virologisk svigt:
14 In the studies of PI-experienced patients, PRO30017 (amprenavir 600 mg / ritonavir 100 mg twice daily in sub-study A and B with 80 and 37 patients respectively), the following mutations emerged in patients with virological failure:
L10F/ I/ V, V11I, I13V, K20R, V32I, L33F, E34Q, M36I, M46I/ L, I47V, G48V, I50V, I54L/ M/ T/ V, Q58E, D60E, I62V, A71V, V77I, V82A/ I, I84V, I85V, L90M og I93L/ M.
L10F/ I/ V, V11I, I13V, K20R, V32I, L33F, E34Q, M36I, M46I/ L, I47V, G48V, I50V, I54L/ M/ T/ V, Q58E, D60E, I62V, A71V, V77I, V82A/ I, I84V, I85V, L90M and I93L/ M.
Følgende mutationer blev påvist hos de patienter, der fik virologsik svigt i løbet af 96 uger:
In the studies of PI-experienced patients, APV30003 and its extension, APV30005 (fosamprenavir 700 mg / ritonavir 100 mg twice daily: n=107), the following mutations emerged in patients experiencing virological failure through 96 weeks:
L10F/ I, L24I, V32I, L33F, M36I, M46I/ L, I47V, I50V, I54L/ M/ S, A71I/ T/ V, G73S, V82A, I84V og L90M.
L10F/ I, L24I, V32I, L33F, M36I, M46I/ L, I47V, I50V, I54L/ M/ S, A71I/ T/ V, G73S, V82A, I84V, and L90M.
Der belv fundet 22 isolater med virologisk svigt og heraf havde ni patienter proteasemutationer, der var opstået som følge af behandling.
In the paediatric studies APV20003 and APV29005, 67 PI-experienced patients were treated with fosamprenavir / ritonavir and of 22 virological failure isolates genotyped, nine patients were found with treatment-emergent protease mutations.
Mutationprofilen var magen til den set hos voksne patienter, der tidligere har været behandlet med PI’ er, behandlet med fosamprenavir/ ritonavir.
The mutational profiles were similar to those described for PI-experienced adults treated with fosamprenavir / ritonavir.
Analyser baseret på genotype- resistens- test Genotypiske fortolkningssystemer kan bruges til at bestemme aktiviteten af amprenavir/ ritonavir eller fosamprenavir/ ritonavir hos personer med PI- resistente isolater.
Genotypic interpretation systems may be used to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in subjects with PI-resistant isolates.
Den nuværende (Juli 2006) ANRS AC- 11- algoritme for fosamprenavir/ ritonavir definerer resistens som tilstedeværelsen af mutationerne V32I+I47A/ V, eller I50V eller mindst fire af følgende mutationer:
The current (July 2006) ANRS AC-11 algorithm for fosamprenavir / ritonavir defines resistance as the presence of the mutations V32I+I47A/ V, or I50V, or at least four mutations among:
Den er forbundet med øget fænotyperesistens over for fosamprenavir i kombination med ritonavir samt som reduceret sandsynlighed for virologisk respons (resistens).
L10F/ I/ V, L33F, M36I, I54A/ L/ M/ S/ T/ V, I62V, V82A/ C/ F/ G, I84V and L90M and is associated with increased phenotypic resistance to fosamprenavir with ritonavir as well as reduced likelihood of virological response (resistance).
Analyser baseret på fænotype- resistens- test Klinisk validerede fænotypiske fortolkningssystemer kan bruges i tilknytning til genotypiske data til at bestemme aktiviteten af amprenavir/ ritonavir eller fosamprenavir/ ritonavir hos patienter med PI - resistente isolater.
Clinically validated phenotypic interpretation systems may be used in association with the genotypic data to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in patients with PI- resistant isolates.
Firmaer, der resistenstester og diagnostiserer, har udviklet klinisk fænotypiske ” cut - offs ” for FPV/ RTV, som kan bruges til at fortolke resultater fra resistenstest.
Resistance testing diagnostic companies have developed clinical phenotypic cut-offs for FPV/ RTV that can be used to interpret resistance test results.
HIV- 1- isolater med en nedsat følsomhed over for amprenavir er selekteret efter en række in vitro - passager.
HIV-1 isolates with a decreased susceptibility to amprenavir have been selected during in vitro serial passage experiments.
Nedsat følsomhed over for amprenavir var associeret med virus, som havde udviklet I50V, I84V, V32I+I47V eller I54M- mutationer.
Reduced susceptibility to amprenavir was associated with virus that had developed I50V or I84V or V32I+I47V or I54M mutations.
Mønstrene ses enten alene eller i kombination med andre mutationer.
There are currently data on cross-resistance between amprenavir and other protease inhibitors for all 4 fosamprenavir resistance pathways, either alone or in combination with other mutations.
Baseret på data fra 25 antiviral- naive patienter, der er blevet behandlet med et svigtende fosamprenavirregime (hvoraf én udviste resistens over for lopinavir og saquinavir ved baseline og en anden over for tipranavir), frembringer resistensmønstret, som er forbundet med amprenavir, begrænset krydsresistens over for atazanavir/ ritonavir (tre ud af 25 isolater), darunavir/ ritonavir (fire ud af 25 isolater), indinavir/ ritonavir (en ud af 25 isolater), lopinavir/ ritonavir (tre ud af 24 isolater), saquinavir (tre ud af 24 isolater) og tipranavir/ ritonavir (fire ud af 24 isolater).
Based on data from twenty-five antiretroviral naïve patients failing a fosamprenavir containing regimen (one of whom showed Baseline resistance to lopinavir and saquinavir and another to tipranavir) the resistance pathways associated with amprenavir produce limited cross-resistance to atazanavir/ ritonavir (three of 25 isolates), darunavir/ ritonavir (four of 25 isolates), indinavir/ ritonavir (one of 25 isolates), lopinavir/ ritonavir (three of 24 isolates), saquinavir (three of 24 isolates) and tipranavir/ ritonavir (four of 24 isolates)..
Den bevarede aktivitet afhænger af antallet og typen af protease- resistente mutationer i isolaterne.
Conversely amprenavir retains activity against some isolates with resistance to other PIs and this retained activity would depend on the number and type of protease resistance mutations present in the isolates
15 Antallet af mutationer, der har betydning for PI- resistens, øges væsentligt, jo længere et regime med svigtende proteasehæmmere fortsættes.
The number of key PI-resistance mutations increases markedly the longer a failing PI-containing regimen is continued.
Krydsresistens mellem amprenavir og revers transkriptasehæmmere er usandsynlig, da angrebspunktet på enzymet er forskellig.
15 Cross resistance between amprenavir and reverse transcriptase inhibitors is unlikely to occur because the enzyme targets are different.
PI- tilvænnede voksne behandlet med boostede Agenerase kapsler
PI-experienced adults, boosted Agenerase capsules
PRO30017 er et randomiseret, åbent studie, hvor PI- tilvænnede voksne, der havde haft virologisk svigt (viral load ≥ 1000 kopier/ ml), fik enten Agenerase (600 mg to gange daglig) i kombination med ritonavir (100 mg to gange daglig) og nukleosidanaloger (NRTI) eller standardbehandling (SOC) med en PI som regel boostet med en lav dosis RTV.
The evidence of efficacy of Agenerase in combination with ritonavir 100 mg twice daily is based on study PRO30017, a randomized, open-label study, in which PI-experienced adults experiencing virological failure (viral load ≥ 1000 copies/ ml) received either Agenerase (600 mg twice daily) in combination with ritonavir (100 mg twice daily) and nucleoside analogues (NRTI) or a standard of care (SOC) PI, predominantly boosted with low-dose RTV.
Patienterne havde alle virus, der var følsomme over for Agenerase, mindst en anden PI og mindst en NRTI.
One hundred and sixty-three (163) patients with virus sensitive to Agenerase, at least one other PI, and at least one NRTI were included in PRO30017 substudy A.
Der blev anvendt en non- inferioritetsmargin på 0, 4 log10 kopier/ ml.
The primary analysis assessed the non- inferiority of APV/ r to the SOC PI group with respect to time-weighted average change from baseline (AAUCMB) in plasma viral load (HIV-1 RNA) at week 16 using a non-inferiority margin of 0.4 log10 copies/ ml.
16 Resultater ved uge 16
16 Results at week 16
Amprenavir / ritonavir
Amprenavir / ritonavir
Forskel mellem
Treatment
(n = 80)
(n = 80)
Indinavir / RTV (29%)
Indinavir / RTV (29%) Lopinavir / RTV (36%) Saquinavir / RTV(20%)
behandlingerne
difference
Lopinavir / RTV (36%) Saquinavir / RTV (20%) Baselinekarakteristika Median HIV- 1- RNA (log10 kopier/ ml) (interval)
Median HIV-1 RNA (log10 copies/ ml) (range)
Median CD4 (celler/ ml) (interval)
Median CD4 (cells/ ml) (range)
Antal af tidligere anvendte PI’ er [n (%)]
Prior number of PIs taken [n (%)]
1 2 ≥3 Median antal af
1 2 ≥ 3 Median number of PI
primære PI- mutationer 1
primary mutations 1 Prior number of NRTIs
1, 0 (interval 0 - 2)
1.0 (range 0-2)
Antal af tidligere anvendte NRTI’ er [n (%)] ≥ 4 Resultat a
taken [n (%)] ≥ 4 Outcomes a
Middel plasma HIV- 1 -
Mean plasma HIV-1
RNA AAUCMB (log10 kopier/ ml)
RNA AAUCMB (log10 copies/ ml)
Plasma HIV- 1 RNA under 400 kopier/ ml (%) a
Plasma HIV-1 RNA below 400 copies/ ml (%) a
6 (−21; 9) c
6 (− 21, 9)c
” Intent To Treat ” (Exponeret) - population:
Intent To Treat (Exposed) Population:
Observeret analyse b Middelstratificeret forskel c 95% konfidensinterval 1 Primære mutationer var, som defineret af IAS USA på det oprindelige analysetidspunkt i 2002; D30N, M46I/ L, G48V, I50V, V82A/ F/ T/ S, I84V, L90M.
Observed analysis b Mean stratified difference c 95% confidence interval 1 Primary mutations were as defined by the IAS USA at the time of the original analysis, 2002 D30N, M46I/ L, G48V, I50V, V82A/ F/ T/ S, I84V, L90M.
Børn tidligere stærkt medicinerede, behandlet med ikke- boostet Agenerase
Heavily pre-treated children, unboosted Agenerase
152 af de 288 børn var tidligere behandlet med PI’ er.
The evidence of efficacy of unboosted Agenerase was based on two uncontrolled clinical studies involving 288 HIV infected children aged between 2 and 18 years, 152 of whom were PI experienced.
Studiet undersøgte Agenerase oral opløsning og kapsler ved doser på 15 mg/ kg tre gange daglig, 20 mg/ kg tre gange daglig, 20 mg/ kg to gange daglig og 22, 5 mg/ kg to gange daglig, selv om flertallet fik 20 mg/ kg to gange daglig.
The studies evaluated Agenerase oral solution and capsules at doses of 15 mg/ kg three times daily, 20 mg/ kg three times daily, 20 mg/ kg twice daily and 22.5 mg/ kg twice daily although the majority received 20 mg/ kg twice daily.
Flertallet af de PI - tilvænnede patienter havde tidligere været behandlet med mindst en (78%) eller to (42%) af de NRTI’ er, der blev administeret samtidig med Agenerase.
Concomitant low dose ritonavir was not administered and the majority of the PI experienced subjects had prior exposure to at least one (78%) or two (42%) of the NRTIs co-administered with Agenerase.
Ved uge 48 havde cirka 25% af patienterne plasma HIV- 1- RNA < 10, 000 kopier/ ml og 9% < 400 kopier/ ml med en medianændring fra baseline i CD4+- celletal på 26 celler/ mm3 (n = 74).
At Week 48, approximately 25% of those enrolled had plasma HIV-1 RNA < 10,000 copies/ ml and 9% < 400 copies/ ml with a median change from baseline in CD4+ cells of 26 cells/ mm3 (n=74).
På baggrund af disse data bør fordelen ved behandling med ikke- boostet Agenerase nøje overvejes, når behandlingen af PI- tilvænnede børn skal optimeres.
Based on these data, careful consideration should be given to the expected benefit of unboosted Agenerase when optimising therapy for PI experienced children.
17 5. 2 Farmakokinetiske egenskaber
17 5.2 Pharmacokinetic properties
Amprenavir absorberes hurtigt og godt efter peroral administration.
Absorption: after oral administration, amprenavir is rapidly and well absorbed.
Cirka 90% af en oral administreret strålemærket amprenavir dosis blev udskilt i urinen og fæces, primært som amprenavir metabolitter.
Approximately 90% of an orally administered radiolabelled amprenavir dose was recovered in the urine and the faeces, primarily as amprenavir metabolites.
0, 5 til 1 time for den orale opløsning.
Following oral administration, the mean time (tmax) to maximal serum concentrations of amprenavir is between 1-2 hours for the capsule and 0.5 to 1 hour for the oral solution.
Ved terapeutiske doser (1200 mg 2 gange daglig) er den maksimale gennemsnitlige steady state koncentration (Cmax, ss) for amprenavir kapsler 5, 36 μg/ ml (0, 92- 9, 81), og den minimale steady state koncentration (Cmin, ss) er 0, 28 μg/ ml (0, 12- 0, 51).
At therapeutic dosages (1200 mg twice daily), the mean maximum steady state concentration (Cmax, ss) of amprenavir capsules is 5.36 µg/ ml (0.92-9.81) and the minimum steady state concentration (Cmin, ss) is 0.28 µg/ ml (0.12-0.51).
AUC over et doseringsinterval på 12 timer er i gennemsnit 18, 46 μg. · h/ ml (3, 02- 32, 95).
The mean AUC over a dosing interval of 12 hours is 18.46 µg. h/ ml (3.02- 32.95).
14% og 19% lavere (se afsnit 4. 2).
The bioavailability of the oral solution at equivalent doses is lower than that of the capsules, with an AUC and Cmax approximately 14% and 19% lower, respectively (see section 4.2).
AUC og Cmin for amprenavir blev forøget med henholdsvis 64% og 508% og Cmax blev nedsat med 30%, når ritonavir (100 mg 2 gange daglig) blev administreret sammen med amprenavir (600 mg 2 gange daglig) sammenlignet med værdier opnået efter indgift af amprenavir i doseringen 1200 mg 2 gange daglig.
The AUC and Cmin of amprenavir were increased by 64% and 508% respectively and the Cmax decreased by 30% when ritonavir (100 mg twice daily) was coadministered with amprenavir (600 mg twice daily) compared to values achieved after 1200 mg twice daily doses of amprenavir.
Selv om administration af amprenavir sammen med mad giver en reduktion af AUC på 25%, har det ingen virkning på koncentrationen af amprenavir 12 timer efter indtagelse (C12).
While administration of amprenavir with food results in a 25% reduction in AUC, it had no effect on the concentration of amprenavir 12 hours after dosing (C12).
Så selv om mad påvirker både absorptionsgraden og - hastigheden, påvirkes den minimale steady state koncentration (Cmin, ss) ikke af fødeindtagelse.
Therefore, although food affects the extent and rate of absorption, the steady-state trough concentration (Cmin, ss) was not affected by food intake.
430 liter (6 l/ kg ved estimeret legemsvægt på 70 kg), hvilket indikerer et stort fordelingsvolumen ved at amprenavir nemt trænger ud i væv uden for den systemiske cirkulation.
Distribution: the apparent volume of distribution is approximately 430 litres (6 l/ kg assuming a 70 kg body weight), suggesting a large volume of distribution, with penetration of amprenavir freely into tissues beyond the systemic circulation.
Koncentrationen af amprenavir i cerebrospinalvæsken er mindre end 1% af plasmakoncentrationen.
The concentration of amprenavir in the cerebrospinal fluid is less than 1% of plasma concentration.
90%.
In in vitro studies, the protein binding of amprenavir is approximately 90%.
Amprenavir er primært bundet til alfa- 1- syreglycoprotein (AAG), men også til albumin.
Amprenavir is primarily bound to the alpha-1-acid glycoprotein (AAG), but also to albumin.
Mængden af ubundet amprenavir, som er den aktive del, er dog formentlig uændret.
This change will decrease the total active substance concentration in the plasma, however the amount of unbound amprenavir, which is the active moiety, is likely to be unchanged.
Mens den absolutte koncentration af frit aktivt stof forbliver konstant, svinger procenten af frit aktivt stof direkte med den totale koncentration af aktivt stof ved steady state og går fra Cmax, ss til Cmin, ss i løbet af doseringsintervallet.
While absolute free active substance concentrations remain constant, the percent of free active substance will fluctuate directly with total active substance concentrations at steady-state go from Cmax, ss to Cmin, ss over the course of the dosing interval.
Amprenavir metaboliseres hovedsageligt i leveren, og mindre end 3% udskilles uomdannet i urinen.
Metabolism: amprenavir is primarily metabolised by the liver with less than 3% excreted unchanged in the urine.
Lægemidler, som inducerer, hæmmer eller er substrater for CYP3A4, skal derfor bruges med forsigtighed, hvis de gives sammen med Agenerase (se afsnit 4. 3, 4. 4 og 4. 5).
Therefore, medicinal products that are inducers, inhibitors or substrates of CYP3A4 must be used with caution when administered concurrently with Agenerase (see sections 4.3, 4.4 and 4.5).
Halveringstiden for plasmaeliminationen af amprenavir ligger fra 7, 1 til 10, 6 timer.
Elimination: the plasma elimination half-life of amprenavir ranges from 7.1 to 10.6 hours.
Den primære eliminationsvej af amprenavir er hepatisk metabolisme med under 3% udskilt
The primary route of elimination of amprenavir is via hepatic metabolism with less than 3% excreted unchanged in the urine.
75% i fæces.
18 account for approximately 14% of the administered amprenavir dose in the urine, and approximately 75% in the faeces.
Farmakokinetikken af amprenavir hos børn (fra 4 år) svarer til den hos voksne.
Paediatrics: the pharmacokinetics of amprenavir in children (4 years of age and above) are similar to those in adults.
Doseringer med Agenerase kapsler 20 mg/ kg 2 gange daglig og 15 mg/ kg 3 gange daglig medførte lignende daglige plasmakoncentrationer af amprenavir som dem, der blev opnået ved dosering af 1200 mg 2 gange daglig til voksne.
Dosages of 20 mg/ kg twice a day and 15 mg/ kg three times a day with Agenerase capsules provided similar daily amprenavir exposure to 1200 mg twice a day in adults.
Agenerase kapsler og oral opløsning kan derfor ikke erstatte hinanden på basis af milligram til milligram.
Amprenavir is 14% less bioavailable from the oral solution than from the capsules; therefore, Agenerase capsules and Agenerase oral solution are not interchangeable on a milligram per milligram basis.
Farmakokinetikken af amprenavir er ikke undersøgt hos patienter over 65 år.
Elderly: the pharmacokinetics of amprenavir have not been studied in patients over 65 years of age.
Patienter med nedsat nyrefunktion er ikke undersøgt specifikt.
Renal impairment: patients with renal impairment have not been specifically studied.
Mindre end 3% af den terapeutiske dosis af amprenavir udskilles uomdannet i urinen.
Less than 3% of the therapeutic dose of amprenavir is excreted unchanged in the urine.
Farmakokinetikken af amprenavir er signifikant ændret hos patienter med moderat til svært nedsat leverfunktion.
Hepatic impairment: the pharmacokinetics of amprenavir are significantly altered in patients with moderate to severe hepatic impairment.
Dosis bør derfor nedsættes til disse patienter (se afsnit 4. 2).
The dosage should therefore be reduced in these patients (see section 4.2).
Disse doser svarede til 2, 0 gange (for mus) og 3, 8 gange (for rotter) de doser, der gives til mennesker ved en dosering på 1200 mg amprenavir 2 gange daglig.
In long-term carcinogenicity studies with amprenavir in mice and rats, there were benign hepatocellular adenomas in males at exposure levels equivalent to 2.0-fold (mice) or 3.8-fold (rats) those in humans given 1200 mg twice daily of amprenavir alone.
Forandringer i det hepatocellulære focus sås i hanmus ved doser på 275 mg/ kg/ dag og 500 mg/ kg/ dag (mindst 2, 0 gange større end den humane terapeutiske dosis).
In male mice altered hepatocellular foci were seen at doses that were at least 2.0 times human therapeutic exposure.
Mekanismen for de hepatocellulære adenoma og carcinomer, som blev fundet i disse undersøgelser er ikke klarlagt og betydningen for mennesker af de observeres effekter er usikker, men data fra kliniske forsøg og fra brug efter markedsføringen om anvendelse hos mennesker tyder på, at disse data har klinisk betydning.
However, there is little evidence from the exposure data in humans, both in clinical trials and from marketed use, to suggest that these findings are of clinical significance.
19 Der fandtes ingen lokal toksicitet eller noget sensibiliseringspotentiale i dyreundersøgelser, men der er set let øjenirritation hos kaniner.
Local toxicity and sensitising potential was absent in animal studies, but slight irritating properties to the rabbit eye were identified.
Toksicitetsundersøgelser hos unge dyr, som blev behandlet fra de var 4 dage gamle, resulterede i høj mortalitet hos både kontroldyr og dem, der fik amprenavir.
19 Toxicity studies in young animals, treated from four days of age, resulted in high mortality in both the control animals and those receiving amprenavir.
Disse resultater antyder, at unge dyr mangler fuldt udviklede metaboliseringsveje, der gør dem i stand til at udskille amprenavir eller nogle kritiske bestanddele af formuleringen (f. eks. propylenglycol, PEG 400).
These results imply that young animals lack fully developed metabolic pathways enabling them to excrete amprenavir or some critical components of the formulation (e. g. propylene glycol, PEG 400).
Hos drægtige mus, kaniner og rotter sås ingen større påvirkning af den embryo- føtale udvikling.
In pregnant mice, rabbits and rats there were no major effects on embryo-foetal development.
Det anbefales derfor, at kvinder i den fertile alder, som får Agenerase, anvender effektiv svangerskabsforebyggelse (f. eks. barrieremetoder).
It is therefore recommended that women of child-bearing potential taking Agenerase should practice effective contraception (e. g. barrier methods).
Kapselskal: gelatine, glycerol, opløsning af d- sorbitol (E420) og sorbitaner, titandioxid, rødt prægeblæk.
Capsule shell: gelatin, glycerol, d-sorbitol (E420) and sorbitans solution, titanium dioxide, red printing ink.
Kapselindhold: d- alfatocopherylpolyethylenglycol 1000 succinat (TPGS), macrogol 400 (PEG 400), propylenglycol.
Capsule contents: d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), macrogol 400 (PEG 400), propylene glycol.
Må ikke opbevares over 30ºC.
Do not store above 30°C.
Hvide High Density Polyethylene (HDPE) - beholdere med 480 kapsler.
White High Density Polyethylene (HDPE) bottles containing 480 capsules.
Glaxo Group Ltd Glaxo Wellcome House Berkeley Avenue Greenford Middlesex UB6 0NN Storbritannien
Glaxo Group Ltd Glaxo Wellcome House Berkeley Avenue Greenford Middlesex UB6 0NN United Kingdom
20. oktober 2000 Fornyelse af tilladelsen:
20 October 2000 Date of last renewal:
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMEAs) hjemmeside http: // www. emea. europa. eu
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu.
Hjælpestoffer: d- sorbitol (E420)
Sorbitol (E420)
Aflange, uigennemsigtige, off- white til flødefarvede og mærket "GX CC2".
Oblong, opaque, off-white to cream coloured, printed with ‘ GX CC2’.
Agenerase, i kombination med andre antiretrovirale mindler, er indiceret til behandling af HIV- 1 - inficerede voksne og børn over 4 år, som tidligere er behandlet med proteasehæmmere (PI’ er).
Agenerase, in combination with other antiretroviral agents, is indicated for the treatment of protease inhibitor (PI) experienced HIV-1 infected adults and children above the age of 4 years.
Den anbefalede dosis Agenerase kapsler er 20 mg/ kg legemsvægt 2 gange daglig i kombination med andre antiretrovirale midler, uden at den totale daglige dosis overstiger 2400 mg.
22 Children (4 to 12 years) and patients less than 50 kg body weight: the recommended dose of Agenerase capsules is 20 mg/ kg body weight twice a day, in combination with other antiretroviral agents, without exceeding a total daily dose of 2400 mg (see section 5.1).
23 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
23 4.4 Special warnings and precautions for use
Brugen af Agenerase kapsler i kombination med ritonavir er kontraindiceret hos patienter med svært nedsat leverfunktion (se afsnit 4. 3).
Agenerase capsules are contraindicated in patients with severe hepatic impairment when used in combination with ritonavir (see section4.3).
24 Forsigtighed er tilrådet ved samtidig brug af Agenerase og delavirdin (se afsnit 4. 5).
Caution is advised when Agenerase is used concomitantly with delavirdine (see section 4.5).