natgillin/translations-raw huggingface dataset:
Boostede proteasehæmmere, såsom darunavir/ ritonavir, udviser en højere resistensbarriere sammenlignet med andre grupper af antiretrovirale stoffer.
Boosted protease inhibitors, like darunavir/ ritonavir, show a higher barrier to resistance compared to other classes of antiretrovirals.
Breakpoints for reduceret aktivitet med etravirin (> 2 etravirin- associerede mutationer ved baseline, se afsnittet om kliniske resultater) gør sig gældende, når etravirin gives i kombination med en boostet proteasehæmmer.
The breakpoints for reduced efficacy with etravirine (> 2 etravirine-associated mutations at baseline, see clinical results section) applies when etravirine is given in combination with a boosted protease inhibitor.
Denne grænse er muligvis lavere ved antiretroviral kombinationsterapi, som ikke inkluderer en boostet proteasehæmmer.
This breakpoint might be lower in antiretroviral combination therapy not including a boosted protease inhibitor.
I fase III- forsøgene DUET- 1 og DUET- 2 var de mutationer, som oftest blev udviklet hos patienter med virologisk svigt over for INTELENCE- regimet V108I, V179F, V179I, Y181C og Y181I, som normalt opstod sammen med flere andre NNRTI- resistensassocierede mutationer (RAM).
In the Phase III trials DUET-1 and DUET-2, mutations that developed most commonly in patients with virologic failure to the INTELENCE containing regimen were V108I, V179F, V179I, Y181C and Y181I, which usually emerged in a background of multiple other NNRTI resistance-associated mutations (RAMs).
I samtlige andre forsøg med INTELENCE til HIV- 1- inficerede patienter var følgende mutationer de mest almindelige:
In all the other trials conducted with INTELENCE in HIV-1 infected patients, the following mutations emerged most commonly:
L100I, E138G, V179F, V179I, Y181C og H221Y.
L100I, E138G, V179F, V179I, Y181C and H221Y.
Krydsresistens Efter virologisk svigt af et etravirinregime bør patienterne ikke behandles med efavirenz og/ eller nevirapin.
Cross-resistance Following virologic failure of an etravirine-containing regimen it is not recommended to treat patients with efavirenz and/ or nevirapine.
Klinisk erfaring Behandlingserfarne patienter Pivotaleforsøg Evidensen for effekten af INTELENCE er baseret på data efter 24 uger fra de to igangværende fase III- forsøg DUET- 1 og DUET- 2.
Clinical experience Treatment-experienced patients Pivotal studies The evidence of efficacy of INTELENCE is based on 24-week data from 2 ongoing Phase III trials DUET-1 and DUET-2.
Disse forsøg har identisk design, og begge forsøg viste nogenlunde samme effekt af INTELENCE.
These trials were identical in design and similar efficacy for INTELENCE was seen in each trial.
13 Forsøgskarakteristika
Trial characteristics
- Design: randomiseret (1: 1), dobbeltblindet, placebokontrolleret.
- Design: randomized (1:1), double-blinded, placebo-controlled.
- Behandling:
- Treatment:
INTELENCE over for placebo ud over et baggrundsregime bestående af
INTELENCE vs. placebo, in addition to a background regimen including
darunavir/ ritonavir (DRV/ rtv), investigatorvalgte N( t) RTI- midler og valgfri enfuvirtid (ENF).
darunavir/ ritonavir (DRV/ rtv), investigator-selected N(t)RTIs and optional enfuvirtide (ENF).
HIV- 1- virusmængde i plasma > 5. 000 HIV- 1 RNA kopier/ ml ved screening én eller flere NNRTI- resistensassocierede mutationer ved screening eller fra tidligere genotypeanalyse (dvs. arkiveret resistens)
HIV-1 plasma viral load > 5000 HIV-1 RNA copies/ml at screening 1 or more NNRTI resistance-associated mutations (RAMs) at screening or from prior genotypic analysis (i.e., archived resistance)
tre eller flere primære proteasehæmmermutationer ved screening stabilt antiretroviralt regime i de sidste 8 uger
3 or more primary PI mutations at screening on a stable antiretroviral regimen for at least 8 weeks.
- Stratificering:
- Stratification:
Randomiseringen blev stratificeret efter beregnet brug af ENF i baggrundsregimet
Randomisation was stratified by the intended use of ENF in the BR, previous use
(BR), tidligere brug af darunavir og virusbelastningen ved screening.
of darunavir and screening viral load.
- Virologisk respons blev defineret som konfirmeret upåviselig virusmængde (< 50 HIV- 1 RNA
(< 50 HIV-1 RNA copies/ml).
Poolede data efter 24 uger fra DUET- 1 og DUET- 2 Baselinekarakteristika
DUET-1 and DUET-2 pooled 24-week data Baseline characteristics
Behandlingsforskel (95% CI)
Treatment difference (95% CI)
Median HIV - 1 RNA i plasma Mediant CD4- celletal Resultater Konfirmeret upåviselig virusmængde (< 50 HIV- 1 RNA kopier/ ml) a n (%)
Median plasma HIV-1 RNA Median CD4 cell count Outcomes Confirmed undetectable viral load (< 50 HIV-1 RNA copies/ml)a n (%)
4, 8 log10 kopier/ ml 99 x 106 celler/ l
4.8 log10 copies/ml 99 x 106 cells/l
4, 8 log10 kopier/ ml 109 x 106 celler/ l
4.8 log10 copies/ml 109 x 106 cells/l
(5, 8%; 15, 4%) f 22, 7%
(5.8%; 15.4%)f 22.7%
< 400 HIV- 1 RNA kopier/ ml n (%) HIV- 1 RNA log10 gennemsnitlig
(16.4%; 29.1%) f a < 400 HIV-1 RNA copies/ml
445 (74, 3%)
445 (74.3%)
21, 8% (16, 5%; 27, 1%) d - 0, 54
21.8%
ændring fra baseline (log10 kopier/ ml) b
n (%) (16.5%; 27.1%)d HIV-1 RNA log10 mean change
(- 0, 71; - 0, 37) c
-0.54
CD4- celletal gennemsnitlig ændring fra baseline (x 106/ l) b Enhver AIDS- definerende sygdom og/ eller død n (%) a
from baseline (log10 copies/ml)b CD4 cell count mean change from baseline (x 106/l)b Any AIDS defining illness and/or
+85, 6 22 (3, 7%)
22 (3.7%)
+66, 8 41 (6, 8%)
41 (6.8%)
+19, 6 (8, 4; 30, 7) c - 3, 1% (- 5, 6%; - 0, 6%) e
(-5.6%; -0.6%)e
P- værdi < 0, 0001 for gennemsnitlig reduktion i HIV- 1 RNA.
Imputations according to the TLOVR algorithm (TLOVR = Time to Loss of Virologic Response). b Non-completer is failure (NC = F) imputation. c Treatment differences are based on Least Square Means from an ANCOVA model including the stratification factors.
P- værdi fra CMH- test, der kontrollerer for stratificeringsfaktorer = 0, 427 for de novo, og < 0, 0001 for ikke de novo.
P-value < 0.0001 for mean decrease in HIV-1 RN A; P-value = 0.0060 for mean change in CD4 cell count. d Confidence interval around observed difference of response rates; P-value < 0.0001 from logistic regression model, including stratification factors. e Confidence interval around observed difference of response rates; P-value = not significant. f Confidence interval around observed difference of response rates; P-value from CMH test controlling for stratification factors = 0.427 for de novo, and < 0.0001 for not de novo.
Eftersom der var en signifikant interaktionseffekt mellem behandlingen og ENF, blev den primære analyse udført for to ENF- strata (patienter, som igen brugte eller ikke brugte ENF, over for patienter,
Since there was a significant interaction effect between treatment and ENF, the primary analysis was done for 2 ENF strata (patients reusing or not using ENF versus patients using ENF de novo); results of this analysis (week 24 data) by ENF stratum are shown in the table above.
En undergruppeanalyse af det virologiske respons (defineret som en virusmængde på < 50 HIV - 1 RNA kopier/ ml) i uge 24 efter virusmængde ved baseline og CD4- celletal ved baseline (poolede DUET- data) vises i tabellen nedenfor.
A subgroup analysis of the virologic response (defined as a viral load < 50 HIV-1 RNA copies/ml) at week 24 by baseline viral load and baseline CD4 count (pooled DUET data) is presented in the table below.
Poolede data fra DUET- 1 og DUET- 2 Andel af patienter med HIV- 1 RNA < 50 kopier/ ml i uge 24 Undergrupper Hiv- 1 RNA ved baseline
DUET-1 and DUET-2 pooled data Proportion of subjects with HIV-1 RNA < 50 copies/ml at week 24 Subgroups
< 30. 000 kopier/ ml ≥ 30. 000 og < 100. 000 kopier/ ml ≥ 100. 000 kopier/ ml CD4- celletal (x 106/ l) ved baseline
14 Baseline HIV-1 RNA < 30,000 copies/ml ≥ 30,000 and < 100,000 copies/ml ≥ 100,000 copies/ml Baseline CD4 count (x 106/l)
< 50 ≥ 50 og < 200 ≥ 200 og < 350 ≥ 350
< 50 ≥ 50 and < 200 ≥ 200 and < 350 ≥ 350
Imputeringer i henhold til TLOVR- algoritmen (TLOVR = tid til tab af virologisk respons).
Imputations according to the TLOVR algorithm (TLOVR = Time to Loss of Virologic Response)
Analyse af genotype eller fænotype og virologisk resultat ved baseline I DUET- 1 og DUET- 2 var forekomsten ved baseline af tre eller flere af følgende mutationer:
Baseline genotype or phenotype and virologic outcome analyses In DUET-1 and DUET-2, the presence at baseline of 3 or more of the following mutations:
V90I, A98G, L100I, K101E, K101P, V106I, V179D, V179F, Y181C, Y181I, Y181V, G190A og G190S (INTELENCE- resistensassocierede mutationer) forbundet med nedsat virologisk respons på INTELENCE (se tabellen nedenfor).
V90I, A98G, L100I, K101E, K101P, V106I, V179D, V179F, Y181C, Y181I, Y181V, G190A and G190S, (INTELENCE RAMs) was associated with a decreased virologic response to INTELENCE (see table below).
Disse individuelle mutationer opstod ved tilstedeværelse af andre NNRTI- resistensassocierede mutationer.
These individual mutations occurred in the presence of other NNRTI RAMs.
Konklusionerne vedrørende relevansen af bestemte mutationer eller mutationsmønstre kan ændres, når der fremkommer yderligere oplysninger, og det anbefales altid at konsultere de aktuelle fortolkningssystemer ved analyse af testresultater for resistens.
Conclusions regarding the relevance of particular mutations or mutational patterns are subject to change with additional data, and it is recommended to always consult current interpretation systems for analysing resistance test results.
Andel af patienter med < 50 HIV- 1 RNA kopier/ ml i uge 24 efter baselineantal af INTELENCE - resistensassocierede mutationer i populationen, som ikke omfattede patienter uden virologisk svigt i puljede data fra DUET- 1 og DUET- 2
Proportion of subjects with < 50 HIV-1 RNA copies/ml at week 24 by baseline number of INTELENCE RAMs in the non-viral failure excluded population of pooled DUET-1 and DUET-2 trials
Antal INTELENCE - resistensassocierede mutationer * ved baseline
Baseline number of
Etraviringrupper N = 549
INTELENCE RAMs*
Brugte igen/ brugte ikke ENF
Reused/not used ENF
Alle 0 1 2 ≥3
ranges 0 1 2 ≥3
Placebogrupper N = 569
Placebo arms N=569
områder
ranges
Alle patienter i DUET- forsøgene modtog et baggrundsregime bestående af darunavir/ rtv, investigatorvalgte NRTI - midler og valgfri enfuvirtid.
* INTELENCE RAMs = V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, G190A/S Note: all patients in the DUET trials received a background regimen consisting of darunavir/rtv, investigator-selected NRTIs and optional enfuvirtide.
K103N som eneste mutation var den mest prævalente NNRTI- mutation i DUET- 1 og DUET- 2 ved baseline og blev ikke identificeret som en INTELENCE- resistensassocieret mutation.
The presence of K103N alone, which was the most prevalent NNRTI mutation in DUET-1 and DUET-2 at baseline, was not identified as a mutation associated with resistance to INTELENCE.
Der
Furthermore, the presence of this mutation alone did not affect the response in the INTELENCE arm.
15 kræves yderligere data for at vurdere indflydelsen fra K103N i forbindelse med mutationer ved andre NNRTI’ er.
Additional data is required to conclude on the influence of K103N when associated with other NNRTIs mutations.
Data fra DUET- forsøgene tyder på, at fold- ændringen (FC) i EC50 over for etravirin ved baseline var en prædiktiv faktor for virologisk resultat med gradvist reduceret respons observeret over FC 3 og FC 13.
Data from the DUET studies suggest that baseline fold change (FC) in EC50 to etravirine was a predictive factor of virologic outcome, with gradually decreasing responses observed above FC 3 and FC 13.
FC- undergrupperne er baseret på de udvalgte patientpopulationer i DUET- 1 og DUET- 2 og er ikke beregnet til at repræsentere definitive kliniske følsomhedsbreakpoints for INTELENCE.
FC subgroups are based on the select patient populations in DUET-1 and DUET-2 and are not meant to represent definitive clinical susceptibility breakpoints for INTELENCE.
Eksplorativ” head to head ” - sammenligning med proteasehæmmer (PI) hos PI- naive patienter (forsøg TMC125- C227) TMC125- C227 var et eksplorativt, randomiseret, aktivt kontrolleret åbent forsøg, som havde til formål at undersøge effekten og sikkerheden af INTELENCE i et behandlingsregime, som ikke er godkendt under den aktuelle indikation.
Exploratory head to head comparison with protease inhibitor in protease inhibitor naïve patients (trial TMC125-C227) TMC125-C227 was an exploratory, randomised, active-controlled open-label trial, which investigated the efficacy and safety of INTELENCE in a treatment regimen, which is not approved under the current indication.
I TMC125- C227- forsøget blev INTELENCE (N = 59) indgivet sammen med to investigatorvalgte NRTI- midler (dvs. uden en ritonavir- boostet PI) og sammenlignet med en investigatorvalgt kombination af én PI med to NRTI- midler (N = 57).
In the TMC125-C227 study, INTELENCE (N=59) was administered with 15 2 investigator-selected NRTIs (i.e. without a ritonavir-boosted PI) and compared to an investigator-selected combination of a PI with 2 NRTIs (N=57).
Forsøgspopulationen omfattede PI- naive, NNRTI- erfarne patienter med evidens for NNRTI- resistens.
The trial population included PI-naïve, NNRTI-experienced patients with evidence of NNRTI resistance.
I uge 12 var det virologiske respons større i PI- kontrolgruppen (- 2, 2 log10 kopier/ ml fra baseline, n = 53) end i INTELENCE- gruppen (- 1, 4 log10 kopier/ ml fra baseline, n = 40).
At week 12, virologic response was greater in the control-PI arm (-2.2 log10 copies/ml from baseline; n=53) compared to the INTELENCE arm (-1.4 log10 copies/ml from baseline; n=40).
På baggrund af disse forsøgsresultater bør INTELENCE ikke bruges i kombination alene med N( t) RTI- midler til patienter, som har oplevet virologisk svigt med et NNRTI - og et N( t) RTI- regime.
Based on these trial results, INTELENCE is not recommended for use in combination with N(t)RTIs only in patients who have experienced virological failure on an NNRTI- and N(t)RTI-containing regimen.
Dette lægemiddel er godkendt under ” betingede omstændigheder ”.
This medicinal product has been authorised under a so-called “conditional approval” scheme.
Det europæiske Lægemiddelagentur (EMEA) vurderer hvert år ny information vedrørende produktet, og produktresuméet vil om nødvendigt blive opdateret.
The European Medicines Agency (EMEA) will review new information on the product every year and this SPC will be updated as necessary.
Etravirins farmakokinetiske egenskaber er blevet evalueret hos raske voksne forsøgspersoner og hos voksne behandlingserfarne HIV- 1inficerede patienter.
The pharmacokinetic properties of etravirine have been evaluated in adult healthy subjects and in adult treatment-experienced HIV-1 infected patients.
Eksponeringen for etravirin var lavere (35- 50%) hos de HIV- 1inficerede patienter end hos de raske forsøgspersoner.
Exposure to etravirine was lower (35-50%) in HIV-1 infected patients than in healthy subjects.
Absorption Etravirin er ikke tilgængelig i en intravenøs formulering, hvorfor den absolutte biotilgængelighed ikke kendes.
Absorption An intravenous formulation of etravirine is unavailable, thus, the absolute bioavailability of etravirine is unknown.
Hos raske forsøgspersoner påvirkes absorptionen af etravirin ikke af samtidig indgift af oral ranitidin eller omeprazol, som øger den gastriske pH- værdi.
In healthy subjects, the absorption of etravirine is not affected by co-administration of oral ranitidine or omeprazole, medicinal products that are known to increase gastric pH.
50%, når INTELENCE blev indgivet i fastende tilstand sammenlignet med indgift efter et måltid.
Effect of food on absorption The systemic exposure (AUC) to etravirine was decreased by about 50% when INTELENCE was administered under fasting conditions, as compared to administration following a meal.
99, 9% bundet til plasmaproteiner, primært til albumin (99, 6%) og α1- syre - glykoprotein (97, 66- 99, 02%) in vitro.
Distribution Etravirine is approximately 99.9% bound to plasma proteins, primarily to albumin (99.6%) and α1-acid glycoprotein (97.66%-99.02%) in vitro.
Fordelingen af etravirin i andre kompartmenter end plasma (f. eks. cerebrospinalvæske, genitalsekreter) er ikke evalueret hos mennesker.
The distribution of etravirine into compartments other than plasma (e.g., cerebrospinal fluid, genital tract secretions) has not been evaluated in humans.
Metabolisme In vitro- forsøg med humane levermikrosomer indikerer, at etravirin primært gennemgår oxidativ metabolisme via det hepatiske cytokrom CYP450- system (CYP3A) og i mindre grad via CYP2C - gruppen efterfulgt af glucuronidation.
Metabolism In vitro experiments with human liver microsomes (HLMs) indicate that etravirine primarily undergoes oxidative metabolism by the hepatic cytochrome CYP450 (CYP3A) system and, to a lesser extent, by the CYP2C family, followed by glucuronidation.
16 Eliminering Efter indgift af en radioaktivt mærket 14C- etravirindosis kunne 93, 7% og 1, 2% af den indgivne 14 C- etravirindosis genfindes i henholdsvis fæces og urin.
Elimination After administration of a radiolabeled 14C-etravirine dose, 93.7% and 1.2% of the administered dose of 14 C-etravirine could be retrieved in faeces and urine, respectively.
81, 2- 86, 4% af den indgivne dosis fandtes uforandret i fæces.
Unchanged etravirine accounted for 81.2% to 86.4% of the administered dose in faeces.
30- 40 timer.
The terminal elimination half-life of etravirine was approximately 30-40 hours.
Særlige populationer Børn Etravirins farmakokinetiske egenskaber hos børn er ved at blive undersøgt.
Special populations Paediatric population The pharmacokinetics of etravirine in paediatric patients are under investigation.
4. 2).
There are insufficient data at this time to recommend a dose (see section 4.2).
4. 2 og 4. 4).
16 Elderly Population pharmacokinetic analysis in HIV infected patients showed that etravirine pharmacokinetics are not considerably different in the age range (18 to 77 years) evaluated, with 6 subjects aged 65 years or older (see sections 4.2 and 4.4).
Køn Der er ikke observeret signifikante farmakokinetiske kønsforskelle.
Gender No significant pharmacokinetic differences have been observed between men and women.
Antallet af kvinder i forsøgene er begrænset.
A limited number of women were included in the studies.
Race En farmakokinetisk populationsanalyse af HIV- inficerede patienter viser ingen synlig forskel i eksponeringen for etravirin mellem hvide, latinamerikanske og sorte forsøgspersoner.
Race Population pharmacokinetic analysis of etravirine in HIV infected patients indicated no apparent difference in the exposure to etravirine between Caucasian, Hispanic and Black subjects.
Nedsat leverfunktion Etravirin metaboliseres og elimineres primært af leveren.
Hepatic impairment Etravirine is primarily metabolised and eliminated by the liver.
Farmakokinetikken af etravirin ændredes ikke hos hverken patienter med let eller moderat nedsat leverfunktion.
In a study comparing 8 patients with mild (Child-Pugh Class A) hepatic impairment to 8 matched controls and 8 patients with moderate (Child-Pugh Class B) hepatic impairment to 8 matched controls, the multiple dose pharmacokinetic disposition of etravirine was not altered in patients with mild to moderate hepatic impairment.
De frie koncentrationer er dog ikke vurderet.
However, unbound concentrations have not been assessed.
Forhøjet eksponering af den frie del kan muligvis forventes.
Increased unbound exposure could be expected.
4. 2 og 4. 4).
INTELENCE has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and is therefore not recommended (see sections 4.2 and 4.4).
Samtidig infektion med hepatitis B - og/ eller hepatitis C- virus Den farmakokinetiske populationsanalyse i DUET- 1 og DUET- 2 viste nedsat clearance (som potentielt kan føre til forøget eksponering og ændring af sikkerhedsprofilen) af INTELENCE hos HIV- 1inficerede patienter, som samtidig var inficeret med hepatitis B - og/ eller hepatitis C- virus.
Hepatitis B and/or hepatitis C virus co-infection Population pharmacokinetic analysis of the DUET-1 and DUET-2 trials showed reduced clearance (potentially leading to increased exposure and alteration of the safety profile) for INTELENCE in HIV-1 infected patients with hepatitis B and/or hepatitis C virus co-infection.
4. 4 og 4. 8).
In view of the limited data available in hepatitis B and/or C co-infected patients, particular caution should be paid when INTELENCE is used in these patients (see sections 4.4 and 4.8).
Nedsat nyrefunktion Etravirins farmakokinetiske egenskaber er ikke undersøgt hos patienter med nyreinsufficiens.
Renal impairment The pharmacokinetics of etravirine have not been studied in patients with renal insufficiency.
Resultater fra et massebalanceforsøg med radioaktivt mærket 14C- etravirin viste, at < 1, 2% af den indgivne etravirindosis udskilles med urinen.
Results from a mass balance study with radioactive 14C-etravirine showed that < 1.2% of the administered dose of etravirine is excreted in the urine.
4. 2).
As etravirine is highly bound to plasma proteins, it is unlikely that it will be significantly removed by haemodialysis or peritoneal dialysis (see section 4.2).
Hæmoragisk kardiomyopati blev kun observeret hos mus af hankøn og blev betragtet som sekundær til svær koagulopati medieret
Haemorrhagic cardiomyopathy was only observed in male mice and was considered to be secondary to severe coagulopathy mediated via the vitamin K pathway.
8 gange højere end den humane eksponering ved den anbefalede dosis (200 mg b. i. d.).
In the dog, changes were observed in the liver and gall bladder at exposures approximately 8-fold higher than human exposure observed at the recommended dose (200 mg b.i.d.).
I et forsøg med rotter var der ingen effekt på parring eller fertilitet ved eksponeringsniveauer svarende til humane eksponeringsniveauer ved den klinisk anbefalede dosis.
In a study conducted in rats, there were no effects on mating or fertility at exposure levels equivalent to those in humans at the clinically recommended dose.
Der var ingen teratogenicitet med etravirin hos rotter eller kaniner ved eksponeringer svarende til humane eksponeringsniveauer ved den anbefalede kliniske dosis.
There was no teratogenicity with etravirine in rats and rabbits at exposures equivalent to those observed in humans at the recommended clinical dose.
Etravirin havde ingen effekt på afkommets udvikling under amning eller efter afvænning ved maternelle eksponeringer, som svarer til humane eksponeringsniveauer ved den anbefalede kliniske dosis.
Etravirine had no effect on offspring development during lactation or post weaning at maternal exposures equivalent to those observed at the recommended clinical dose.
Cancerogenitetsforsøg med etravirin til gnavere er igangværende.
17 Carcinogenicity studies of etravirine in rodents are ongoing.
In vitro - og in vivo- forsøg med etravirin har ikke vist evidens for mutagent potentiale.
In vitro and in vivo studies with etravirine revealed no evidence of a mutagenic potential.
Plasticglas af højdensitetspolyethylen (HDPE) indeholdende 120 tabletter og tre poser med tørremiddel forsynet med børnesikret låg af polypropylen (PP).
High-density polyethylene (HDPE) plastic bottles containing 120 tablets and 3 desiccant pouches, fitted with polypropylene (PP) child resistant closures.
Janssen- Cilag International NV Turnhoutseweg 30 B- 2340 Beerse Belgien
Janssen-Cilag International NV Turnhoutseweg 30 B-2340 Beerse Belgium
< DD, MM, ÅÅÅÅ > < DD, måned, ÅR >
< {DD/MM/YYYY} > < {DD month YYYY} >
Yderligere information om dette lægemiddel er tilgængelig på Det Europæiske Lægemiddelagenturs (EMEA' s) 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/
Janssen 04010 Borgo San Michele Latina Italien
Janssen 04010 Borgo San Michele Latina Italy