natgillin/translations-raw huggingface dataset:
4. 4).
If Kivexa has been discontinued in patients due to experiencing any one of these symptoms and a decision is made to restart a medicinal product containing abacavir, this must be done in a setting where medical assistance is readily available (see section 4.4).
Der er meget sjældne rapporter om erythema multiforme, Stevens- Johnsons syndrom eller toksisk epidermal nekrolyse, hvor overfølsomhed over for abacavir ikke kunne udelukkes.
Very rarely cases of erythema multiforme, Stevens- Johnson syndrome or toxic epidermal necrolysis have been reported where abacavir hypersensitivity could not be ruled out.
I disse tilfælde bør behandling med abacavir ophøre permanent.
In such cases medicinal products containing abacavir should be permanently discontinued.
Frekvenser er defineret som meget almindelig (> 1/ 10), almindelig (> 1/ 100, < 1/ 10), ikke almindelig (> 1/ 1. 000, < 1/ 100), sjælden (> 1/ 10. 000, < 1/ 1. 000) og meget sjælden (< 1/ 10. 000).
Frequencies are defined as very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1000 ,< 1/100), rare (> 1/ 10,000, < 1/ 1000), very rare (< 1/ 10,000).
Organklasse
Body system
Abacavir
Abacavir
Blod og lymfesystem
lymphatic systems
Neutropeni og anæmi (begge af og til alvorlige), trombocytpeni Meget sjælden:
anaemia (both occasionally severe), thrombocytopenia Very rare:
Immunsystemet Metabolisme og ernæring
Immune system disorders
Almindelig:
Common: hypersensitivity
Overfølsomhed Almindelig:
Common: anorexia
Hovedpine, søvnløshed Meget sjælden:
Very rare:
Tilfælde af perifer neuropati (eller paræstesi) er rapporteret
Cases of peripheral neuropathy (or paraesthesia) have been reported
Luftveje, thorax og mediastinum
10 Respiratory, thoracic and mediastinal disorders
Hoste, symptomer fra næse
Cough, nasal symptoms
Mave- tarmkanalen Lever og galdeveje
Gastrointestinal disorders
Pancreatitis er rapporteret, men kausale relationer til abacavir behandling er usikre
Common: nausea, vomiting, diarrhoea Rare: pancreatitis has been reported, but a causal relationship to abacavir treatment is uncertain
Kvalme, opkastning, mavesmerter eller – kramper, diarré Sjælden:
Nausea, vomiting, abdominal pain or cramps, diarrhoea Rare:
Stigning i serum amylase.
Rises in serum amylase.
Tilfælde af pancreatitis er blevet rapporteret Ikke almindelig:
Cases of pancreatitis have been reported
Midlertidige stigninger af leverenzymer (ASAT, ALAT) Sjælden:
Transient rises in liver enzymes (AST, ALT), Rare:
Erythema multiforme, Stevens- Johnsons syndrom og toksisk epidermal nekrolyse
Common: rash (without systemic symptoms) Very rare: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis
Feber, svær udmatning, træthed
Common: fever, lethargy, fatigue.
Træthed, utilpashed, feber
Common: fatigue, malaise, fever.
4. 4).
Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, have been reported with the use of nucleoside analogues (see section 4.4).
4. 4).
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 (see section 4.4).
11 Særligt hos patienter med generelt anerkendte risikofaktorer, fremskreden HIV- sygdom eller langvarig kombinationsbehandling med antiretrovirale lægemidler (CART) er der rapporteret om tilfælde af osteonekrose.
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 (CART).
4. 8), og symptomatisk behandling iværksættes om nødvendigt.
If overdose occurs the patient should be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary.
5. 1 Farmakodynamiske egenskaber Farmakoterapeutisk klassifikation:
Pharmacotherapeutic group:
Antiretrovirale lægemidler mod HIV- infektioner, kombinationstyper.
Antivirals for treatment of HIV infections, combinations.
J05A R02.
J05AR02.
Abacavir og lamivudin er NRTI’ er og er potente selektive hæmmere af HIV- 1 og HIV- 2.
Abacavir and lamivudine are NRTIs, and are potent selective inhibitors of HIV- 1 and HIV-2.
Både abacavir og lamivudin bliver metaboliseret sekventielt ved intracellulære kinaser til de respektive 5 ’ - triphosphater (TP), som er de aktive dele.
Both abacavir and lamivudine are metabolised sequentially by intracellular kinases to the respective 5'-triphosphate (TP) which are the active moieties.
Lamivudin- TP og carbovir- TP (den aktive trifosfat form af abacavir) er substrater for og kompetitive hæmmere af HIV revers transkriptase (RT).
Lamivudine-TP and carbovir-TP (the active triphosphate form of abacavir) are substrates for and competitive inhibitors of HIV reverse transcriptase (RT).
Men deres centrale antivirale aktivitet sker ved inkorporering af monofosfatformen ind i den virale DNA kæde, resulterende i en kædetermination.
However, their main antiviral activity is through incorporation of the monophosphate form into the viral DNA chain, resulting in chain termination.
Abacavir og lamivudin trifosfater viser signifikant mindre affinitet for værtcelle DNA polymeraser.
Abacavir and lamivudine triphosphates show significantly less affinity for host cell DNA polymerases.
Lamivudin har vist sig at være meget synergistisk med zidovudin, hvor det hæmmer replikationen af HIV i cellekulturer.
Lamivudine has been shown to be highly synergistic with zidovudine, inhibiting the replication of HIV in cell culture.
Abacavir udviser synergi in vitro i kombination med nevirapin og zidovudin.
Abacavir shows synergy in vitro in combination with amprenavir, nevirapine and zidovudine.
Stoffet er vist at være additivt i kombination med didanosin, stavudin og lamivudin.
It has been shown to be additive in combination with didanosine, stavudine and lamivudine.
In vitro- resistens:
In-vitro resistance:
HIV- 1 resistens over for lamivudin involverer udviklingen af M1841 - eller, hvad der er mere almindeligt, M184V- aminosyreændringer tæt ved den aktive del af viral RT.
HIV-1 resistance to lamivudine involves the development of a M184I or, more commonly, M184V amino acid change close to the active site of the viral RT.
Der er påvist abacavirresistente isolater af HIV- 1 in vitro, som er forbundet med specifikke genotypeforandringer i RT- codonregionen (codoner M184V, K65R, L74V og Y115F).
Abacavir-resistant isolates of HIV-1 have been selected in vitro and are associated with specific genotypic changes in the RT codon region (codons M184V, K65R, L74V and Y115F).
In vivo- resistens (behandlingsnaive patienter):
In vivo resistance (Therapy-naïve patients):
M184V - eller M1841- varianter opstår hos HIV- 1- positive patienter, der behandles med lamivudin- holdige antiretroviraler.
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing antiretroviral therapy.
Isolater fra patienter, som har haft virologisk svigt under en behandling med abacavir i pivotale kliniske forsøg, viste i de fleste tilfælde enten ingen NRTI- relaterede ændringer i forhold til baseline (45%) eller kun M184V - eller M1841- mutationer (45%).
Isolates from most patients experiencing virological failure with a regimen containing abacavir in pivotal clinical trials showed either no NRTI-related changes from baseline (45%) or only M184V or M184I selection (45%).
Mindre almindelig var mutationerne L74V (5%), K65R (1%) og Y115F (1%) (se tabel).
The overall selection frequency for M184V or M184I was high (54%), and less common was the selection of L74V (5%), K65R (1%) and Y115F (1%) (see Table).
Når zidovudin inkluderes i behandlingen med abacavir, reduceres forekomsten af L74V - og K65R - mutationerne (med zidovudin:
The inclusion of zidovudine in the regimen has been found to reduce the frequency of L74V and K65R selection in the presence of abacavir (with zidovudine:
0/ 40, uden zidovudin:
0/ 40, without zidovudine:
12 Behandling
Therapy
Abacavir + Combivir1
Abacavir +
Abacavir + lamivudin +
lamivudine +
Abacavir + lamivudin + PI
PI (or
(eller PI/ ritonavir)
PI/ ritonavir) Number of
Antal forsøgspersoner
Subjects
Antal virologiske svigt
Number of Virological Failures Number of On-
Antal genotyper i behandling
Therapy
41 (100%)
141 (100%)
K65R L74V Y115F M184V/ I TAM’ er3
L74V Y115F
1 Combivir er en fastdosiskombination af lamivudin og zidovudin 2 Omfatter tre ikke- virologiske svigt og fire ubekræftede, virologiske svigt 3 Antal forsøgspersoner med ≥1 thymidinanaloge mutationer (TAM’ er)
Number of subjects with ≥ 1 Thymidine Analogue Mutations (TAMs).
TAM’ er kan opstå, når thymidinanaloger anvendes sammen med abacavir.
TAMs might be selected when thymidine analogs are associated with abacavir.
I en metaanalyse med seks kliniske forsøg sås ingen TAM’ er i behandlingsregimerne med abacavir uden zidovudin (0/ 127), men der blev påvist TAM’ er i behandlingsregimerne indeholdende abacavir og thymidinanalogen zidovudin (22/ 86, 26%).
In a meta-analysis of six clinical trials, TAMs were not selected by regimens containing abacavir without zidovudine (0/ 127), but were selected by regimens containing abacavir and the thymidine analogue zidovudine (22/ 86, 26%).
In vivo- resistens (tidligere behandlede patienter):
In vivo resistance (Therapy experienced patients):
M184V - eller M1841- varianterne opstår hos HIV- 1 - positive patienter, der er behandlet med lamivudin- holdige antiretroviraler og giver høj resistens over for lamivudin.
The M184V or M184I variants arise in HIV-1 infected patients treated with lamivudine-containing antiretroviral therapy and confer high-level resistance to lamivudine.
Ved fremkomst af M184V tyder in vitro- data på, at lamivudin stadig har antiretroviral aktivitet (formentlig på grund af svækkede vira).
In vitro data tend to suggest that the continuation of lamivudine in anti- retroviral regimen despite the development of M184V might provide residual anti-retroviral activity (likely through impaired viral fitness).
Behandling med andre NRTI’ er vil under alle omstændigheder være at foretrække frem for at fortsætte behandling med lamivudin.
In any case, initiation of susceptible NRTIs should always be preferred to maintenance of lamivudine therapy.
Ved fremkomst af M184V- mutationer bør man kun overveje at fortsætte med lamivudin i de tilfælde, hvor der ikke længere er andre virksomme NRTI’ er.
Therefore, maintaining lamivudine therapy despite emergence of M184V mutation should only be considered in cases where no other active NRTIs are available.
123 (74%) ud af de 166 forsøgspersoner havde M184V/ I, 50 (30%) havde T215Y/ F, 45 (27%) havde M4IL, 30 (18%) havde K70R og 25 (15%) havde D67N.
In a meta-analysis of five clinical trials where ABC was added to intensify therapy, of 166 subjects, 123 (74%) had M184V/ I, 50 (30%) had T215Y/ F, 45 (27%) had M41L, 30 (18%) had K70R and 25 (15%) had D67N.
K65R blev ikke fundet, og L74V og Y115F forekom sjældent (≤ 3%).
K65R was absent and L74V and Y115F were uncommon (≤ 3%).
Den logistiske regressionsmodel for den prædiktive værdi af genotype (justeret for baseline- plasma HIV- 1- RNA [vRNA], CD4+- celletal, antal og varighed af tidligere antiretrovirale behandlinger) viste, at tilstedeværelsen af 3 eller flere NRTI- resistens- forbundne mutationer var forbundet med nedsat respons i uge 4 (p = 0, 015) eller 4 eller flere mutationer ved median uge 24 (p ≤ 0, 012).
Logistic regression modelling of the predictive value for genotype (adjusted for baseline plasma HIV-1RNA [vRNA], CD4+ cell count, number and duration of prior antiretroviral therapies) showed that the presence of 3 or more NRTI resistance-associated mutations was associated with reduced response at Week 4 (p=0.015) or 4 or more mutations at median Week 24 (p≤ 0.012).
Ydermere kan 69- indsættelseskomplekset eller Q151M- mutationen, sædvanligvis fundet i kombination med A62V, V751, F77L og F116Y, forårsage et højt niveau af resistens over for abacavir.
In addition, the 69 insertion complex or the Q151M mutation, usually found in combination with A62V, V75I, F77L and F116Y, cause a high level of resistance to abacavir.
13
Week 4
Revers transkriptase -
Baseline Reverse Transcriptase
Uge 4
Median
(n = 166)
(n = 166) Percent with
Median ændring vRNA (log10 c/ ml)
Change vRNA (log10 c/ mL)
Procent med < 400 pr. ml vRNA
< 400 copies/ mL vRNA
Ingen M184V alene En NRTI- mutation To NRTI- forbundne mutationer
None
15 75 82 22
15
- 0, 96 - 0, 74 - 0, 72 - 0, 82
associated mutations Any three NRTI-
40 64 65 32
32%
Tre NRTI- forbundne mutationer
associated mutations Four or more NRTI-
Fire eller flere NRTI - forbundne mutationer
associated mutations
Fænotyperesistens og krydsresistens:
Phenotypic resistance and cross-resistance:
Fænotyperesistens over for abacavir kræver M184V med mindst en anden abacavir- mutation eller M184V med flere TAM’ er.
Phenotypic resistance to abacavir requires M184V with at least one other abacavir-selected mutation, or M184V with multiple TAMs.
Fænotypisk krydsresistens over for andre NRTI’ er med kun M184V - eller M1841- mulationen er begrænset.
Phenotypic cross- resistance to other NRTIs with M184V or M184I mutation alone is limited.
Tilstedeværelsen af M184V sammen med K65R giver mulighed for krydsresistens mellem abacavir, tenofovir, didanosin og lamivudin.
The
Ligeledes kan tilstedeværelsen af M184V sammen med L74V være årsag til krydsresistens mellem abacavir, didanosin og lamivudin.
13 presence of M184V with K65R does give rise to cross-resistance between abacavir, tenofovir, didanosine and lamivudine, and M184V with L74V gives rise to cross-resistance between abacavir, didanosine and lamivudine.
Krydsresistens mellem abacavir eller lamivudin og antiretroviraler fra andre grupper, f. eks.
Cross-resistance between abacavir or lamivudine and antiretrovirals from other classes e. g.
PI’ er eller NNRTI’ er, er usandsynlig
PIs or NNRTIs is unlikely.
Terapinaive patienter Kombinationen af abacavir og lamivudin som et én gang dagligt regime er støttet af et 48 ugers multi - center, dobbelblindt, kontrolleret forsøg (CNA30021) af 770 HIV- inficerede, terapinaive voksne.
Therapy-naïve patients The combination of abacavir and lamivudine as a once daily regimen is supported by a 48 weeks multi-centre, double-blind, controlled study (CNA30021) of 770 HIV-infected, therapy-naïve adults.
Disse var primært asymptomatiske HIV- inficerede patienter (CDC stadie A).
These were primarily asymptomatic HIV infected patients (CDC stage A).
De blev randomiseret til at modtage enten abacavir (ABC) 600 mg én gang daglig eller 300 mg to gange daglig i kombination med lamivudin 300 mg én gang daglig og efavirenz 600 mg én gang daglig.
They were randomised to receive either abacavir (ABC) 600 mg once daily or 300 mg twice daily, in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily.
Resultaterne er sammenfattet i tabellen nedenfor:
The results are summarised in the table below:
Virologisk Respons Baseret på Plasma HIV- 1 RNA < 50 kopier/ ml ved uge 48 ITT- Eksponeret Population
Virological Response Based on Plasma HIV-1 RNA < 50 copies/ ml at Week 48 ITT-Exposed Population
Behandlings regime
Treatment regimen
ABC én/ dag
ABC once/ day
ABC to/ dag
ABC twice/ day
(N = 384)
(N = 384)
(N = 386)
(N = 386)
Virologisk respons
Virological response
1. 7, 95% CI - 8. 4, 4. 9) blev observeret for begge regimer.
Similar clinical success (point estimate for treatment difference: -1.7, 95% CI – 8.4, 4.9) was observed for both regimens.
Ud fra disse resultater kan det konkluderes med 95% konfidens at den sande forskel ikke er større end 8. 4% til fordel for to gange daglig regimet.
From these results, it can be concluded with 95% confidence that the true difference is no greater than 8.4% in favour of the twice daily regimen.
Denne potentielle forskel er tilstrækkelig lille til at drage en overordnet konklusion om ikke- inferioritet af abacavir én gang daglig over for abacavir to gange daglig.
This potential difference is sufficiently small to draw an overall conclusion of non-inferiority of abacavir once daily over abacavir twice daily.
14 Der var en lav, ensartet virusbyrde (udgangsværdi > 50 kopier/ ml) i både en gang daglig og to gange daglig behandlingsgrupperne (henholdsvis 10% og 8%).
There was a low, similar overall incidence of virologic failure (viral load > 50 copies/ ml) in both the once and twice daily treatment groups (10% and 8% respectively).
I den lille sample størrelse for genotypeanalyse var der en tendens mod en større hyppighed af NRTI- associerede mutationer i én gang daglig versus to gange daglig abacavir regimet.
In the small sample size for genotypic analysis, there was a trend toward a higher rate of NRTI-associated mutations in the once daily versus the twice daily abacavir regimens.
Ingen holdbar konklusion kunne drages ud fra de begrænsede data fra dette forsøg.
No firm conclusion could be drawn due to the limited data derived from this study.
Tidligere behandlede patienter I studie CAL30001 blev 182 tidligere behandlede patienter med virologisk svigt randomiseret og de modtag enten Kivexa én gang daglig eller abacavir 300 mg to gange daglig plus lamivudin 300 mg én gang daglig, begge i kombination med tenofovir og en PI eller en NNRTI i 48 uger.
Therapy-experienced patients In study CAL30001, 182 treatment-experienced patients with virologic failure were randomised and received treatment with either Kivexa once daily or abacavir 300 mg twice daily plus lamivudine 300 mg once daily, both in combination with tenofovir and a PI or an NNRTI for 48 weeks.
Resultater indikerer at Kivexagruppen var ikke- inferiør over for gruppen med abacavir to gange daglig baseret på ensartede reduktioner i HIV- 1 RNA målt som det gennemsnitlige areal under kurven minus baseline (AAUCMB, henholdsvis - 1, 65 log10 kopier/ ml versus - 1, 83 log10 kopier/ ml, 95% CI - 0, 13, 0, 38).
Results indicate that the Kivexa group was non-inferior to the abacavir twice daily group, based on similar reductions in HIV-1 RNA as measured by average area under the curve minus baseline (AAUCMB, - 1.65 log10 copies/ ml versus -1.83 log10 copies/ ml respectively, 95% CI -0.13, 0.38).
Forholdet mellem HIV- 1 RNA < 50 kopier/ ml (50% versus 47%) og < 400 kopier/ ml (54% versus 57%) var ligeledes ensartet i hver gruppe (ITT population).
Proportions with HIV-1 RNA < 50 copies/ ml (50% versus 47%) and < 400 copies/ ml (54% versus 57%) were also similar in each group (ITT population).
I studie ESS30008 blev 260 patienter, med virologisk suppression på et ” first line ” terapiregime bestående af abacavir 300 mg plus lamivudin 150 mg begge givet 2 gange daglig og en PI eller NNRTI, randomiseret til at fortsætte dette regime eller at skifte til Kivexa plus PI eller NNRT i 48 uger.
Results
Resultaterne indikerer at Kivexagruppen kunne associeres med et ensartet virologisk udfald (ikke- inferiør) sammenlignet med abacavir plus lamivudin gruppen baseret på forholdet mellem individer med HIV- 1 RNA < 50 kopier/ ml (henholdsvis 90% og 85%, 95% CI - 2. 7, 13. 5).
14 indicate that the Kivexa group was associated with a similar virologic outcome (non-inferior) compared to the abacavir plus lamivudine group, based on proportions of subjects with HIV-1 RNA < 50 copies/ ml (90% and 85% respectively, 95% CI -2.7, 13.5).
Fastdosiskombinationstabletten af abacavir/ lamivudin (FDC) er vist at være bioækvivalent med lamivudin og abacavir administreret separat.
The fixed-dose combination tablet of abacavir/ lamivudine (FDC) has been shown to be bioequivalent to lamivudine and abacavir administered separately.
Dette blev demonstreret i en enkeltdosis, 3- vejs overkrydsningsbioækvivalensforsøg med FDC (fastende) versus 2 x 300 mg abacavir tabletter plus 2 x 150 mg lamivudin tabletter (fastende) mod FDC givet med et måltid med højt fedtindhold til raske frivillige (n=30).
This was demonstrated in a single dose, 3-way crossover bioequivalence study of FDC (fasted) versus 2 x 300 mg abacavir tablets plus 2 x 150 mg lamivudine tablets (fasted) versus FDC administered with a high fat meal, in healthy volunteers (n = 30).
Disse resultater indikerer at FDC kan tages med eller uden mad.
These results indicate that FDC can be taken with or without food.
Abacavir og lamivudin absorberes hurtigt og godt fra mavetarmkanalen efter oral administration.
Abacavir and lamivudine are rapidly and well absorbed from the gastro-intestinal tract following oral administration.
Den absolutte biotilgængelighed af oral abacavir og lamivudin hos voksne er henholdsvis omkring 83% og 80 - 85%.
The absolute bioavailability of oral abacavir and lamivudine in adults is about 83% and 80-85% respectively.
Efter peroral indgift er gennemsnitstiden (tmax) for at opnå maksimal serumkoncentration (Cmax) omkring 1, 5 time og 1, 0 time for henholdsvis abacavir og lamivudin.
The mean time to maximal serum concentrations (tmax) is about 1.5 hours and 1.0 hour for abacavir and lamivudine, respectively.
Efterfølgende en enkeltdosis af 600 mg abacavir er (CV) Cmax 4, 26 µg/ ml (28%) og (CV) AUC∞ er 11, 95 µg. t/ ml (21%).
Following a single dose of 600 mg of abacavir, the mean (CV) Cmax is 4.26 µg/ ml (28%) and the mean (CV) AUC∞ is 11.95 µg. h/ ml (21%).
Efterfølgende flerdosis oral administration af lamivudin 300 mg én gang daglig i syv dage er (CV) steady- state Cmax 2, 04 µg/ ml (26%) og (CV) AUC24 er 8, 87 µg. t/ ml (21%).
Following multiple-dose oral administration of lamivudine 300 mg once daily for seven days, the mean (CV) steady-state Cmax is 2.04 µg/ ml (26%) and the mean (CV) AUC24 is 8.87 µg. h/ ml (21%).
Intravenøse forsøg med abacavir og lamivudin viste at det gennemsnitlige fordelingsvolumen er henholdsvis 0, 8 og 1, 3 l/ kg.
Intravenous studies with abacavir and lamivudine showed that the mean apparent volume of distribution is 0.8 and 1.3 l/ kg respectively.
In vitro undersøgelser for plasmaproteinbinding indikerer, at abacavir kun i
Plasma protein binding studies in vitro indicate that abacavir binds only low to moderately (~49%) to human plasma proteins at therapeutic concentrations.
Lamivudin udviser lineær farmakokinetik i hele det terapeutiske doseringsinterval med begrænset binding til plasmaprotein in vitro (< 36%).
Lamivudine exhibits linear pharmacokinetics over the therapeutic dose range and displays limited plasma protein binding in vitro (< 36%).
Data viser, at abacavir og lamivudin penetrerer centralnervesystemet (CNS) og når ud i cerebrospinalvæsken CSF).
Data show that abacavir and lamivudine penetrate the central nervous system (CNS) and reach the cerebrospinal fluid (CSF).
Undersøgelser med abacavir demonstrerer et fordelingsforhold mellem CSF og plasma AUC på mellem 30 og 44%.
Studies with abacavir demonstrate a CSF to plasma AUC ratio of between 30 to 44%.
De observerede værdier for maksimale plasmakoncentrationer er 9 gange større end IC50 for abacavir, som er 0, 08 μg/ ml eller 0, 26 μM, når der gives 600 mg abacavir 2 gange daglig.
The observed values of the peak concentrations are 9 fold greater than the IC50 of abacavir of 0.08 µg/ ml or 0.26 µM when abacavir is given at 600 mg twice daily.
12%.
The mean ratio of CSF/ serum lamivudine concentrations 2-4 hours after oral administration was approximately 12%.
2% af den indgivne dosis udskilles uomdannet via nyrerne.
Abacavir is primarily metabolised by the liver with approximately 2% of the administered dose being renally excreted, as unchanged compound.
66% af den administrerede dosis.
The primary pathways of metabolism in man are by alcohol dehydrogenase and by glucuronidation to produce the 5’ -carboxylic acid and 5’ -glucuronide which account for about 66% of the administered dose.
Sandsynligheden for metaboliske interaktioner mellem lamivudin og andre lægemidler er lav på grund af begrænset levermetabolisme (5- 10%) og lav plasmaprotein binding.
The likelihood of metabolic drug interactions with lamivudine is low due to the small extent of hepatic metabolism (5-10%).
Den gennemsnitlige halveringstid af abacavir er ca.
15 The mean half-life of abacavir is about 1.5 hours.