natgillin/translations-raw huggingface dataset:
Enzymet blev oprindelig udvundet fra en svamp, men i Fasturtec produceres det ved en metode, der kaldes ‘ rekombinant DNA- teknologi ’: det fremstilles af en gærart, som har modtaget et gen (DNA), der gør den i stand til at producere uratoxidase.
The enzyme was originally extracted from a fungus, but in Fasturtec it is produced by a method known as ‘ recombinant DNA technology’: it is made by a yeast that has received a gene (DNA) that makes it able to produce urate oxidase.
To af undersøgelserne var udviklet til at fastsætte den bedste dosis.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged standard treatment for reducing uric acid levels) in one of the studies, which included 52 patients.
I denne undersøgelse var det vigtigste mål for effekt mængden af urinsyre i blodet, målt over 96 timer.
In this study, the main measure of effectiveness was the amount of uric acid in the blood, measured over 96 hours.
Hvilken fordel viser undersøgelserne, at der er ved Fasturtec?
What benefit has Fasturtec shown during the studies?
De undersøgelser, der skulle fastsætte den bedste dosis, viste, at Fasturtec efter 48 timer ved en dosis på 0, 20 mg/ kg reducerede mængden af urinsyre i blodet til det normale hos 95% af patienterne.
The dose-finding studies showed that, after 48 hours, Fasturtec at a dose of 0.20 mg/ kg reduced the uric acid levels to normal values in 95% of patients.
I den undersøgelse, der sammenlignede de to forskellige behandlinger, var Fasturtec mere effektiv end allopurinol: i løbet af de første 96 timer efter behandlingen havde de patienter, der var blevet behandlet med Fasturtec, et lavere gennemsnitligt niveau af urinsyre i blodet sammenlignet med de patienter, der var blevet behandlet med allopurinol (henholdsvis 128, 1 og 328, 5 mg. h/ dl).
In the comparative study, Fasturtec was more effective than allopurinol: over the first 96 hours after treatment, patients treated with Fasturtec had a lower average blood level of uric acid compared that in the patients treated with allopurinol (128.1 and 328.5 mg. h/ dl, respectively).
Hvilken risiko er der forbundet med Fasturtec?
What is the risk associated with Fasturtec?
De mest almindelige bivirkninger i forbindelse med Fasturtec (set hos mellem 1 og 10 ud af 100 patienter) er allergiske reaktioner (hovedsagelig udslæt) og feber.
The most common side effects with Fasturtec (seen in between 1 and 10 patients in 100) are allergic reactions, mainly rashes, and fever.
Patienterne bør under behandlingen overvåges nøje for allergiske reaktioner.
Patients should be closely monitored for allergic reactions during treatment.
Den fuldstændige liste over de indberettede bivirkninger ved Fasturtec fremgår af indlægssedlen.
For the full list of all side effects reported with Fasturtec, see the Package Leaflet.
Fasturtec bør ikke anvendes til patienter, der er overfølsomme (allergiske) over for rasburikase eller over for et eller flere af de øvrige indholdsstoffer.
Fasturtec should not be used in patients who are hypersensitive (allergic) to rasburicase or any of the other ingredients.
Fasturtec bør ikke anvendes til patienter med glukose- 6- fosfat- dehydrogenasemangel (G6PD) eller andre metaboliske lidelser, der vides at forårsage hæmolytisk anæmi (blodmangel på grund af for hurtig nedbrydning af de røde blodlegemer).
Fasturtec should not be used in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PD) or other metabolic disorders known to cause haemolytic anaemia (low red blood cell counts, caused by the cells being destroyed too soon).
Hvorfor blev Fasturtec godkendt?
Why has Fasturtec been approved?
Udvalget for Humanmedicinske Lægemidler (CHMP) var af den opfattelse, at Fasturtecs fordele er større end risiciene til behandling og forebyggelse af akut hyperurikæmi for at forebygge akut nyresvigt hos patienter med ondartede hæmatologiske lidelser med stor tumorbelastning og risiko for hastig tumor- lysis eller tumordegradering i begyndelsen af den kemoterapeutiske behandling.
The Committee for Medicinal products for Human Use (CHMP) decided that Fasturtec’ s benefits are greater than its risks for the treatment and prophylaxis of acute hyperuricaemia, in order to prevent acute renal failure, in patients with haematological malignancy with a high tumour burden and at risk of a rapid tumour lysis or shrinkage at initiation of chemotherapy.
Udvalget anbefalede udstedelse af markedsføringstilladelse for Fasturtec.
The Committee recommended that Fasturtec be given marketing authorisation.
Andre oplysninger om Fasturtec:
Other information about Fasturtec:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Fasturtec til sanofi- aventis den 23. februar 2001.
The European Commission granted a marketing authorisation valid throughout the European Union for Fasturtec to sanofi-aventis on 23 February 2001.
Markedsføringstilladelsen blev forlænget den 23. februar 2006.
The marketing authorisation was renewed on 23 February 2006.
Den fuldstændige EPAR for Fasturtec findes her.
The full EPAR for Fasturtec is available here.
Pulver og solvens til
Pharmaceutical form Powder and solvent for solution for infusion
Pulver: hætteglas a 1, 5 mg
Packaging vial (glass); ampoule (glass)
Pulver: hætteglas
1.5 mg; solvent:
3 hætteglas
Package size 3 vials + 3 ampoules
EU/ 1/ 00/ 170/ 002 Fasturtec
EU/ 1/ 00/ 170/ 002
7. 5 mg/ 5 ml
7.5 mg/ 5 ml
Pulver og solvens til Intravenøs anvendelse koncentrat til infusion, opløsning
Powder and solvent for solution for infusion
Pulver: hætteglas a 7, 5 mg Solvens: ampul a 5 ml
vial (glass); ampoule (glass)
Pulver: hætteglas Solvens: ampul (glas)
5 ml (1.5 mg/ ml)
Fasturtec 1, 5 mg/ ml pulver og solvens til koncentrat til infusionsvæske, opløsning.
Fasturtec 1.5 mg/ ml powder and solvent for concentrate for solution for infusion.
Efter rekonstitution indeholder 1 ml Fasturtec 1, 5 mg rasburikase.
After reconstitution, 1 ml of Fasturtec concentrate contains 1.5 mg rasburicase.
Fasturtec er et rekombinant uratoxidaseenzym fremstillet i en genmanipuleret Saccharomyces cerevisiae- stamme.
Fasturtec is a recombinant urate-oxidase enzyme produced by genetically modified Saccharomyces cerevisiae strain.
34 kDa.
Rasburicase is a tetrameric protein with identical subunits of a molecular mass of about 34 kDa.
1 mg svarer til 18, 2 EAU *.
1 mg corresponds to 18.2 EAU*.
* En « enzyme activity unit » (EAU) svarer til den enzymaktivitet, der kan omdanne 1 µmol urinsyre til allantoin per minut under følgende forhold: +30°C±1°C TEA pH 8, 9 buffer.
*One enzyme activity unit (EAU) corresponds to the enzyme activity that converts 1 µmol of uric acid into allantoin per minute under the operating conditions described: +30 °C ± 1 °C TEA pH 8.9 buffer.
4. 1 Terapeutiske indikationer
Therapeutic indications
Behandling og profylakse af akut hyperurikæmi for at forebygge akut nyresvigt hos patienter med maligne hæmatologiske lidelser med højt tumorload og risiko for hastig tumorlyse eller - degradering i begyndelsen af kemoterapeutisk behandling.
Treatment and prophylaxis of acute hyperuricaemia, in order to prevent acute renal failure, in patients with haematological malignancy with a high tumour burden and at risk of a rapid tumour lysis or shrinkage at initiation of chemotherapy.
4. 2 Dosering og indgivelsesmåde
Posology and method of administration
Fasturtec skal indgives under overvågning af en læge med erfaring i kemoterapi af hæmatologiske maligne tilstande.
Fasturtec should be administered under the supervision of a physician trained in chemotherapy of haematological malignancies.
Tilgængelige data tillader ikke anbefaling af gentagne behandlingsserier.
Fasturtec is to be used immediately prior to and during the initiation of chemotherapy only, as at the present, there is insufficient data to recommend multiple treatment courses.
Den anbefalede dosis er 0, 20 mg/ kg/ dag.
The recommended dose for Fasturtec is 0.20 mg/ kg/ day.
Hvis det ikke er muligt at anvende en separat dropslange, skal slangen gennemskylles med saltvandsopløsning mellem infusion af kemoterapeutiske midler og rasburikase.
If use of a separate line is not possible, the line should be flushed out with saline
6. 6.
2 solution between infusion of chemotherapeutic agents and rasburicase.
6. 6.
Because rasburicase may degrade uric acid in vitro, special precautions must be used during sample handling for plasma uric acid measurements, see section 6.6.
Yderligere information om særlige populationer Patienter med nedsat nyre - eller leverfunktion:
Additional information on special populations Renally or hepatically impaired patients:
Eftersom dosisjustering ikke er nødvendig, er den anbefalede dosis 0, 20 mg/ kg/ dag.
As no adjustment is necessary, the recommended dose is 0.20 mg/ kg/ day.
Overfølsomhed over for det aktive indholdsstof eller over for et af hjælpestofferne.
Hypersensitivity to the active substance or to any of the excipients.
G6PD- mangel og andre metaboliske sygdomme, der medfører hæmolytisk anæmi, idet konvertering af urinsyre til allantoin medfører dannelse af biproduktet hydrogenperoxid.
Hydrogen peroxide is a by-product of the conversion of uric acid to allantoin.
I lighed med andre proteiner kan rasburikase fremkalde allergiske reaktioner hos mennesker.
Rasburicase like other proteins, has the potential to induce allergic responses in humans.
I så fald skal Fasturtec omgående seponeres permanent, og en passende behandling iværksættes.
In such cases, treatment should immediately and permanently be discontinued and appropriate therapy initiated.
Der er observeret rasburikase- antistoffer hos behandlede patienter og raske personer, der har fået rasburikase.
Anti-rasburicase antibodies have been detected in treated patients and healthy volunteers administered rasburicase.
4. 8).
Fasturtec should immediately and permanently be discontinued in patients having developed methaemoglobinaemia, and appropriate measures initiated (see section 4.8).
4. 8).
In such case, treatment should immediately and permanently be discontinued and appropriate measures initiated (see section 4.8).
Fasturtec er ikke effektiv i behandlingen af disse tilstande, hvorfor sådanne patienter skal monitoreres tæt.
Therefore, patients must be monitored closely.
Det foreligger ingen data, der kan begrunde sekventiel brug af Fasturtec og allopurinol.
There is no data available to recommend the sequential use of Fasturtec and allopurinol.
6. 6).
To ensure accurate measurement of uric acid plasma level during treatment with Fasturtec, a strict sample handling procedure must be followed (see section 6.6).
Der er ikke foretaget undersøgelser af rasburikases metabolisering.
No metabolism studies have been performed.
Da rasburikase i sig selv er et enzym, anses risikoen for lægemiddelinteraktioner som begrænset.
Rasburicase being an enzyme itself, it would be an unlikely candidate for drug-drug interactions.
3 / 4. 6 Graviditet og amning
3 4.6 Pregnancy and lactation
Der er ingen erfaringer med administration af rasburikase under graviditet.
For rasburicase no clinical data on exposed pregnancies are available.
5. 3.).
Animal studies with respect to effects on parturition and postnatal development have not been performed (see section 5.3).
Den potentielle risiko under tilsvarende humane forhold er således ukendt.
The potential risk for humans is unknown.
Fasturtec bør således ikke anvendes under graviditet eller amning.
Fasturtec should not be used during pregnancy or in breast- feeding women.
Det vides ikke om rasburikase udskilles i brystmælk.
It is unknown whether rasburicase is excreted in human milk.
De væsentligste lægemiddelrelaterede bivirkninger var almindelige allergiske reaktioner og især udslæt og nældefeber.
The most significant drug-related adverse events were common allergic reactions, mainly rashes and urticaria.
Tilfælde af hypotension (< 1%), bronkospasmer (< 1%), rhinitis (< 0, 1%) og alvorlige overfølsomhedsreaktioner (< 1%), inklusive anafylaksi (< 0, 1%), er også sat i forbindelse med Fasturtec.
Cases of hypotension (< 1%), bronchospasm (< 1%), rhinitis (< 0.1%) and severe hypersensitivity reactions (< 1%), including anaphylaxis (< 0.1%) have also been attributed to Fasturtec.
I kliniske forsøg har Fasturtec i usædvanlige tilfælde givet anledning til hæmatologiske sygdomme såsom hæmolyse, hæmolytisk anæmi og methæglobinæmi.
In clinical trials, haematological disorders such as haemolysis, haemolytic anaemia and methaemoglobinaemia are uncommonly caused by Fasturtec.
Enzymatisk omsætning af urinsyre til allantoin ved hjælp af rasburikase giver hydrogenperoxid, og der er observeret hæmolytisk anæmi og methæmoglobinæmi hos visse højrisikopopulationer såsom personer med G6PD- mangel.
The enzymatic digestion of uric acid to allantoin by rasburicase produces hydrogen peroxide and haemolytic anaemia or methaemoglobinaemia have been observed in certain at risk populations such as those with G6PD deficiency.
Endvidere er der nedenfor anført bivirkninger af grad 3 eller 4, der måske skyldes Fasturtec og er fremkommet under kliniske forsøg, opført efter systemorganklasse og hyppighed.
In addition, grade 3 or 4 adverse reactions possibly attributable to Fasturtec and reported in the clinical trials, are listed below, by system organ class and by frequency.
Hyppigheden angives som almindelig (≥ 1/ 100, < 1/ 10) eller usædvanlig (≥ 1/ 1. 000, < 1/ 100).
Frequencies are defined as: common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100).
Hovedpine Diarré
Uncommon Headache Diarrhoea
Opkastning Kvalme Almene symptomer og reaktioner på administrationsstedet.
Gastrointestinal disorders General disorders and administration site conditions
Inden for hver enkelt frekvensgruppe alvorligste skal anføres først.
Vomiting Nausea
De
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
4 / 5.
5.
Afgiftningsmidler ved cytostatica- behandling, ATC- kode:
Detoxifying agents for antineoplastic treatment, ATC code:
V03AF07
V03AF07.
Den akutte stigning i urinsyres plasmaniveauer efter destruktion af et større antal celler, som det ses ved maligne sygdomme og under kemoterapi med cytostatika, kan føre til nedsat nyrefunktion og nyresvigt, hvilket henføres til udfældning af urinsyrekrystaller i tubuli renales.
4 levels of uric acid subsequent to the lysis of large numbers of malignant cells and during cytoreductive chemotherapy may lead to impairment of renal function and renal failure resulting from the precipitation of crystals of uric acid in renal tubules.
Hos raske personer er der observeret et markant dosisafhængigt fald i urinsyres plasmaniveauer i dosisintervallet 0, 05 mg/ kg til 0, 20 mg/ kg.
In healthy volunteers, a marked dose-related decrease in plasma uric acid levels was observed across the dose range 0.05 mg/ kg to 0.20 mg/ kg of Fasturtec.
En randomiseret komparativ fase III- undersøgelse baseret på den anbefalede dosis viste en signifikant hurtigere virkning af Fasturtec sammenlignet med allopurinol.
A randomised comparative phase III study, using the recommended dose, showed a significantly more rapid onset of action of Fasturtec in comparison with allopurinol.
4 timer efter første dosis var der en signifikant forskel i den gennemsnitlige procentvise ændring i forhold til plasmakoncentrationen af urinsyre ved baseline (p < 0, 0001) i gruppen, som fik Fasturtec (- 86%), sammenlignet med allopurinol- gruppen (- 12, 1%).
At 4 hours post first dose, there was a significant difference in the mean percentage change from baseline plasma uric acid concentration (p < 0.0001) in the Fasturtec group (-86.0%) compared to that for the allopurinol group (-12.1%).
Det fører så igen til effektiv udskillelse af serum- phosphatbelastningen, hvilket forebygger yderligere nedsættelse af nyrefunktionen på grund af henfald af calcium/ phosphor.
In turn, this allows efficient excretion of the serum phosphate load preventing further deterioration of renal function from calcium/ phosphorus precipitation.
Pædiatriske patienter I kliniske pivotal studier blev 246 patienter (< 18 år) behandlet med rasburikase i doser på 0, 15 mg/ kg/ dag eller 0, 20 mg/ kg/ dag i 1 til 8 dage (hovedsaglig 5 til 7 dage).
Paediatric patients In pivotal clinical studies, 246 patients (< 18 years) were treated with rasburicase at doses of 0.15 mg/ kg/ day or 0.20 mg/ kg/ day for 1 to 8 days (mainly 5 to 7 days).
Effektiviteten målt på 229 patienter viste en generel responsrate (normalisering af plasma- urinsyre- niveau) på 96, 1%.
Efficacy results on 229 evaluable patients showed an overall response rate (normalization of plasma uric acid levels) of 96.1%.
I langtidssikkerhedsstudier viste en analyse af data fra 867 patienter (< 18 år) som blev behandlet med rasburikase 0, 20 mg/ kg/ dag i 1 til 24 dage (hovedsaglig 1 til 4 dage), resultater, der er forenelige med kliniske pivotal studier med hensyn til effektivitet og sikkerhed.
In long term safety studies, an analysis of data from 867 patients (< 18 years) treated with rasburicase at 0.20 mg/ kg/ day for 1 to 24 days (mainly 1 to 4 days) showed consistent findings with pivotal clinical studies in terms of efficacy and safety.
Efter infusion af rasburikase i doser på 0. 20 mg/ kg/ dag, opnås steady state på dag 2- 3.
After infusion of rasburicase at a dose of 0.20 mg/ kg/ day, steady state is achieved at day 2 - 3.
Der blev ikke observeret ophobning af rasburikase.
No unexpected accumulation of rasburicase was observed.
Hos patienter varierede fordelingsvolumen fra 110 - 127 ml/ kg, hvilket svarer til det fysiologiske vaskulære volumen.
In patients, the volume of distribution ranged from 110 - 127 ml/ kg, which is comparable to the physiological vascular volume.
3, 5 ml/ h/ kg og halveringstiden ca.
3.5 ml/ h/ kg and the elimination half-life ca.
19 timer.
19 hours.
Patienter inkluderet i farmakokinetiske studier var overvejende børn og unge.
The patients included in the pharmacokinetic studies were mainly children and adolescents.
Baseret på begrænsede erfaringer, synes det som om clearance er øget (ca.
Based upon these limited data, it seems that clearance is increased (ca.
35%) hos børn og unge sammenlignet med voksne, førende til lavere eksponering.
35%) in children and adolescents compared to adults, resulting in a lower systemic exposure.
Rasburikase er et protein, hvorfor det:
Rasburicase is a protein, and therefore:
1) ikke forventes at bindes til andre proteiner, 2) forventes at metaboliseres som andre proteiner, hvilket vil sige ved peptidhydrolyse, 3) sandsynligvis ikke vil have interaktioner med andre lægemidler.
1) not expected to bind to proteins, 2) expected that metabolic degradation will follow the pathways of other proteins, i. e. peptide hydrolysis, 3) unlikely to be candidate for drug-drug interactions.
Renal elimination af rasburikase formodes at være beskeden og have ringe betydning for stoffets clearance.
Renal elimination of rasburicase is considered to be a minor pathway for rasburicase clearance.
Da stoffet primært kan forventes at omsættes via peptidhydrolyse, antages nedsat lever funktion ikke at have nævneværdig indflydelse på farmakokinetikken.
As metabolism is expected to occur by peptide hydrolysis, an impaired liver function is not expected to affect the pharmacokinetics.
5 / 5. 3 Prækliniske sikkerhedsdata
5.3 Preclinical safety data
Ikke- kliniske data har ikke afsløret specifikke risici for mennesker i konventionelle studier af farmakologisk sikkerhed, toksikologi og genotoksicitet.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Tolkningen af ikke- kliniske studier begrænses af tilstedeværelsen af endogen uratoxidase i de standardiserede dyreforsøgsmodeller.
The interpretation of the non-clinical studies is hampered due to the presence of endogenous urate oxidase in standard animal models.
Pulver: alanin mannitol dinatriumphosphatdodecahydrat dinatriumphosphatdihydrat natriumdihydrogenphosphatdihydrat.
Powder: alanine mannitol disodium phosphate dodecahydrate disodium phosphate dihydrate sodium dihydrogen phosphate dihydrate
Solvens: poloxamer 188 aqua ad iniectabilia.
Solvent: poloxamer 188 water for injection
På grund af mulighed for proteinaggregation må glukoseopløsning ikke anvendes til fortynding.
Do not use any glucose solution for dilution due to potential incompatibility.
- 3 år.
3 years.
Det er
After reconstitution or dilution an immediate use is recommended.
imidlertid påvist, at holdbarheden efter anbrud er 24 timer ved opbevaring mellem +2°C og 8°C.
However, the in-use stability has been demonstrated for 24 hours between +2 °C and 8 °C.
Pulver i hætteglas: opbevares i køleskab (ved 2°C - 8°C).
Powder in vial: store in a refrigerator (2 °C - 8 °C).
6. 3.
For storage conditions of the reconstituted or the diluted medicinal product, see section 6.3.
6 / 6. 5 Emballagetype og pakningsstørrelser
6.5 Nature and contents of container
3 hætteglas à 1, 5 mg rasburikase og 3 ampuller à 1 ml solvens.
3 vials of 1.5 mg rasburicase and 3 ampoules of 1 ml solvent.
1 hætteglas à 7, 5 mg rasburikase og 1 ampul à 5 ml solvens.
1 vial of 7.5 mg rasburicase and 1 ampoule of 5 ml solvent.
6. 6 Regler for destruktion og anden håndtering
6 6.6 Special precautions for disposal and other handling
Rasburikase skal opløses i hele indholdet i den medfølgende ampul med solvens (hætteglasset med 1, 5 mg rasburikase skal rekonstitueres med 1 ml ampul med solvens – hætteglasset med 7, 5 mg rasburikase skal rekonstitueres med 5 ml ampul med solvens).
Rasburicase must be reconstituted with the entire volume of the supplied solvent ampoule (1.5 mg rasburicase vial to be reconstituted with the 1 ml solvent ampoule; 7.5 mg rasburicase vial to be reconstituted with the 5 ml solvent ampoule).
Rekonstitutionen giver en opløsning med en koncentration på 1, 5 mg/ ml rasburikase, som skal fortyndes yderligere med natriumchlorid 9 mg/ ml (0, 9%) infusionsopløsning.
Reconstitution results in a solution with a concentration of 1.5 mg/ ml rasburicase to be further diluted with sodium chloride 9 mg/ ml (0.9%) intravenous solution.
Medicinen er beregnet til enkeltdosering.
For single-use only, any unused solution should be discarded.
Ikke anvendt opløsning bør bortskaffes.
The solvent contains no preservative.
Den nødvendige mængde færdigblandet opløsning fra et eller flere hætteglas skal fortyndes yderligere med en natriumchloridopløsning 9 mg/ ml (0, 9%) op til et volumen på i alt 50 ml.
The required volume of the reconstituted solution, taken from one or more vials, is to be further diluted with sodium chloride 9 mg/ ml (0.9%) solution to make a total volume of 50 ml.
Da opløsningen ikke indeholder konserveringsmiddel, skal den fortyndede infusionsopløsning indgives omgående.
Therefore the diluted solution should be infused immediately.
Infusion:
Infusion:
Hvis det er nødvendigt at overvåge urinsyreværdier, skal følgende procedurer for håndtering af prøver følges for at undgå ex vivo- nedbrydning.
If it is necessary to monitor a patient’ s uric acid level, a strict sample-handling procedure must be followed to minimise ex vivo degradation of the analyte.
Prøverne nedsænkes i bad med is/ vand.
Samples must be immersed in an ice/ water bath.
Plasmaprøverne tilberedes straks ved centrifugering i en nedkølet centrifuge (4°C).
Plasma samples should immediately be prepared by centrifugation in a pre-cooled centrifuge (4 °C).
Endelig skal plasma opbevares i bad med is/ vand og analyseres for urinsyre inden for 4 timer.
Finally, plasma must be maintained in an ice/ water bath and analysed for uric acid within 4 hours.
7 / 7.
7.
sanofi- aventis 174, avenue de France F- 75013 Paris Frankrig
sanofi-aventis 174, avenue de France F - 75013 Paris France
23. februar 2001 Dato for sidste fornyelse:
23 February 2001 Date of latest renewal:
8 / BILAG II
8 ANNEX II
FREMSTILLER( E) AF DET (DE) BIOLOGISK AKTIVE STOF( FER) OG FREMSTILLERE ANSVARLIG( E) FOR BATCHFRIGIVELSE
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
9 / A.
9 A.