natgillin/translations-raw huggingface dataset:
Europa- Kommissionen udstedte en markedsføringstilladelse for Cerezyme med gyldighed i hele Den Europæiske Union til Genzyme Europe B. V. den 17. november 1997.
The European Commission granted a marketing authorisation valid throughout the European Union for Cerezyme to Genzyme Europe B. V. on 17 November 1997.
Markedsføringstilladelsen blev fornyet den 17. november 2002 og den 17. november 2007.
The marketing authorisation was renewed on 17 November 2002 and on 17 November 2007.
Dette sammendrag blev sidst opdateret i 11- 2007
This summary was last updated in 11-2007.
EU- nummer
EU-number
Paknings - størrelse
Packaging size
Pulver til koncentrat til opløsning til infusion
Powder for concentrate for solution for infusion
5 ml (40E/ ml)
5 ml (40U/ ml)
5 ml( 40E/ ml)
5 ml (40U/ ml)
10 ml (40E/ ml)
10 ml (40U/ ml)
10 ml( 40E/ ml)
10 ml (40U/ ml)
Cerezyme 200 E Pulver til koncentrat til infusionsvæske, opløsning
Cerezyme 200 U Powder for concentrate for solution for infusion
Hvert hætteglas indeholder 200 enheder * imiglucerase **.
Each vial contains 200 units* of imiglucerase**.
Efter rekonstitution indeholder opløsningen 40 enheder imiglucerase pr. ml (200 E/ 5 ml).
After reconstitution, the solution contains 40 units of imiglucerase per ml (200 U/ 5 ml).
* En enzymenhed (E) defineres som den enzymmængde, der katalyserer hydrolysen af et mikromol/ min. af det syntetiske substrat para- nitrofenyl β- D- glucopyranosid (pNP- Glc) ved 37°C. ** modificeret form for glucocerebrosidase produceret i ovarieceller hos kinesisk hamster ved rekombinant DNA- teknologi.
* An enzyme unit (U) is defined as the amount of enzyme that catalyses the hydrolysis of one micromole of the synthetic substrate para-nitrophenyl β -D-glucopyranoside (pNP-Glc) per minute at 37°C. ** modified form of glucocerebrosidase produced in Chinese Hamster Ovary cells by recombinant DNA technology.
Dette lægemiddel indeholder natrium og gives i 0, 9% natriumklorid intravenøs opløsning (se pkt.
This medicinal product contains sodium and is administered in 0.9% sodium chloride intravenous solution (see section 6.6).
6. 6) Efter rekonstitution indeholder opløsningen 0, 62 mmol natrium (200 E/ 5 ml).
After reconstitution, the solution contains 0.62 mmol sodium (200 U/ 5 mL).
Dette skal tages i betragtning hos patienter, der er på en kontrolleret natrium- diæt.
To be taken into consideration by patients on a controlled sodium diet.
Pulver til koncentrat til infusionsvæske, opløsning Cerezyme er et hvidt til off- white pulver.
Cerezyme is a white to off-white powder.
Therapeutiske indikationer
4.1 Therapeutic indications
Cerezyme (imiglucerase) er indiceret til brug som langvarig enzymerstatningsbehandling hos patienter med en bekræftet diagnose lydende på ikke- neuronopatisk (Type 1) eller kronisk neuronopatisk (Type 3) Gauchers sygdom, der udviser klinisk signifikante, ikke- neurologiske manifestationer af sygdommen.
Cerezyme (imiglucerase) is indicated for use as long-term enzyme replacement therapy in patients with a confirmed diagnosis of non-neuronopathic (Type 1) or chronic neuronopathic (Type 3) Gaucher disease and who exhibit clinically significant non-neurological manifestations of the disease.
D- vitaminmangel. • Hepatomegali eller splenomegali.
The non-neurological manifestations of Gaucher disease include one or more of the following conditions: • anaemia after exclusion of other causes, such as iron deficiency • thrombocytopenia • bone disease after exclusion of other causes such as Vitamin D deficiency • hepatomegaly or splenomegaly
Dosering og indgivelsemåde
4.2 Posology and method of administration
Behandlingen bør ske under tilsyn af læger, som er bekendt med behandling af Gaucher’ s sygdom.
Therapy should be directed by physicians knowledgeable in the management of Gaucher disease.
Dosering til voksne, børn og ældre På grund af den heterogene, multisystemiske karakter af Gaucher' s sygdom skal doseringen justeres individuelt for hver patient på baggrund af en komplet vurdering af de kliniske symptomer.
Posology for Adults, Children and Elderly Due to the heterogeneity and the multi-systemic nature of Gaucher disease, dosage should be individualised for each patient based on a comprehensive evaluation of the clinical manifestations of the disease.
En række doseringsregimer har vist sig effektiv over for nogle af eller alle sygdommens ikke - neurologiske manifestationer.
A range of dosage regimens has proven effective towards some or all of the non-neurological manifestations of the disease.
En initialdosering på 60 E/ kg kropsvægt en gang hver anden uge har vist sig at medføre forbedring i hæmatologiske og viscerale parametre inden for et behandlingsforløb
Initial doses of 60 U/ kg of body weight once every 2 weeks have shown
2 på 6 måneder, og fortsat brug har enten standset progression af knoglesygdommen eller resulteret i bedring af denne.
2 improvement in haematological and visceral parameters within 6 months of therapy and continued use has either stopped progression of or improved bone disease.
En dosering helt ned til 2, 5 E/ kg kropsvægt tre gange om ugen eller 15 E/ kg kropsvægt en gang hver anden uge har vist sig at føre til bedring af hæmatologiske parametre og organomegali, men ikke af knogleparametre.
Administration of doses as low as 2.5 U/ kg of body weight three times a week or 15 U/ kg of body weight once every 2 weeks has been shown to improve haematological parameters and organomegaly, but not bone parameters.
De fleste data er baseret på denne infusionshyppighed.
The usual, and for the patient, most convenient frequency of infusion is once every 2 weeks; this is the frequency of infusion for which the most data are available.
Patientrespons skal vurderes rutinemæssigt, og dosis bør kun justeres (opad eller nedad) efter en nøje vurdering af patientrespons i forbindelse med alle sygdommens kliniske symptomer.
Patient responses must be routinely evaluated and dosages should only be adjusted (up or down) based on a comprehensive evaluation of patient response relating to all clinical manifestations of the disease.
Når den individuelle patientrespons for alle de relevante kliniske symptomer er veletableret og stabil, kan dosis justeres med henblik på fortsat effektiv behandling, mens responsparametrene og patientens velbefindende fortsat omhyggeligt observeres.
Once individual patient response for all relevant clinical manifestations is well-established and stabilised, dosages may be adjusted for continued effective therapy, while continuing to closely monitor response parameters and patient well-being.
Kontrol finder sædvanligvis sted med et interval på mellem 6 og 12 måneder.
Usual monitoring intervals range from 6 to 12 months.
5. 1).
The efficacy of Cerezyme on neurological symptoms of chronic neuronopathic Gaucher patients has not been established and no special dosage regimen can be recommended for these manifestations (see section 5.1).
6. 6) gives præparatet ved intravenøs infusion over 1 til 2 timer.
After reconstitution and dilution (see section 6.6) the preparation is administered by intravenous infusion over 1 to 2 hours.
Alternativt kan den passende dosis Cerezyme administreres ved en hastighed, der ikke overstiger 1 enhed pr. kg legemsvægt pr. minut.
Alternatively, the appropriate dose of Cerezyme may be administered at a rate not exceeding 1 unit per kg body weight per minute.
5. 1).
Medical or healthcare professionals are encouraged to register Gaucher patients, including those with chronic neuronopathic manifestations of the disease, in the “ ICGG Gaucher Registry” (see section 5.1).
4. 4 nedenfor).
Hypersensitivity to the active substance or to any of the excipients (see section 4.4).
15% af de behandlede patienter.
Hypersensitivity Current data suggest that, during the first year of therapy, IgG antibodies to imiglucerase are formed in approximately 15% of the treated patients.
Efter 12 måneders behandling udvikles sjældent antistoffer mod Cerezyme.
It appears that patients who will develop IgG antibody are most likely to do so within 6 months of treatment and will rarely develop antibodies to Cerezyme after 12 months of therapy.
(se pkt.
Patients with antibody to Cerezyme (imiglucerase) have a higher risk of hypersensitivity reactions (see section 4.8).
Som med ethvert intravenøst proteinprodukt er kraftige allergisk- lignende overfølsomhedsreaktioner mulige.
As with any intravenous protein product, severe allergic-type hypersensitivity reactions are possible.
Hvis disse reaktioner forekommer, anbefales en umiddelbar afbrydelse af Cerezyme- infusion og at passende medicinsk behandling indledes.
If these reactions occur, immediate discontinuation of the Cerezyme infusion is recommended and appropriate medical treatment should be initiated.
Pulmonal hypertension Pulmonal hypertension er en kendt komplikation til Gauchers sygdom, som er observeret både hos patienter, der var i enzymsubstitutionsbehandling, og patienter, der ikke var i enzymsubstitutionsbehandling.
It has been observed both in patients receiving and not receiving enzyme replacement therapy.
Der er ikke påvist nogen årsagssammenhæng med enzymsubstitutionsbehandlingen.
No causal relationship with enzyme replacement therapy has been established.
Patienter med åndedrætssymptomer bør undersøges for pulmonal hypertension.
Patients with respiratory symptoms should be evaluated for the presence of pulmonary hypertension.
6. 6).
3 Excipients This medicinal product contains sodium and is administered in 0.9% sodium chloride intravenous solution (see section 6.6).
Graviditet og amning
4.6 Pregnancy and lactation
Der er ikke udført dyreforsøg for at vurdere effekten af Cerezyme på drægtigheden, den embryonale/ føtale udvikling, parturition eller den postnatale udvikling.
No animal studies have been carried out with respect to assessing the effects of Cerezyme on pregnancy, embryonal/ foetal development, parturition and postnatal development.
Der kræves en risk/ benefit- vurdering af hver gravid Gaucher patient, eller patienter som ønsker at blive gravide.
In pregnant Gaucher patients and those intending to become pregnant, a risk-benefit treatment assessment is required for each pregnancy.
Graviditet og kliniske manifestationer af Gauchers sygdom skal følges nøje mhp. individualiseret dosering i henhold til patientens behov og terapeutiske respons.
Close monitoring of the pregnancy and clinical manifestations of Gaucher disease is necessary for the individualization of dose according to the patient ’ s needs and therapeutic response.
Det vides ikke, om den aktive substans udskilles i human mælk, men enzymet fordøjes sandsynligvis i barnets gastrointestinale kanal.
It is not known whether this active substance is excreted in human milk, however, the enzyme is likely to be digested in the child ’ s gastrointestinal tract
Virkninger på evnen til at føre motorkøretøj eller betjene maskiner
4.7 Effects on ability to drive and use machines
Cerezyme har ingen eller ubetydelig indflydelse på evnen til at føre bil eller betjene maskiner.
Cerezyme has no or negligible influence on the ability to drive and use machines.
Bivirkninger
4.8 Undesirable effects
Bivirkninger er angivet efter systemorganklasse og hyppighed (almindelig (≥1/ 100 til < 1/ 10) og ikke almindelig (≥1/ 1000 til < 1/ 100)) i tabellen nedenfor.
Adverse drug reactions are listed by system organ class and frequency (common (≥ 1/ 100 to < 1/ 10) and uncommon (≥ 1/ 1,000 to < 1/ 100)) in the table below.
Inden for hver hyppighedsgruppe vises bivirkninger med faldende alvorlighed.
Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.
4 Nervesystemet Ikke almindelig:
4 Nervous system disorders Uncommon:
Svimmelhed, hovedpine, paræstesi Hjerte Ikke almindelig:
Dizziness, headache, paraesthesia Cardiac disorders Uncommon:
Takykardi, cyanose Vaskulære sygdomme Ikke almindelig:
Tachycardia, cyanosis Vascular disorders
Rødmen, hypotension Luftveje, thorax og mediastinum Almindelig:
Flushing, hypotension
Respiratoriske symptomer Mave- tarmkanalen Ikke almindelig:
Respiratory, thoracic and mediastinal disorders Gastrointestinal disorders
Opkastning, kvalme, diarré, mavekramper Hud og subkutane væv Almindelig:
Musculoskeletal and connective tissue disorders
Urticaria/ angioødem, pruritus, udslæt Knogler, led, muskler og bindevæv Ikke almindelig:
Urticaria/ angioedema, pruritus, rash
Artralgi Almene symptomer og reaktioner på administrationsstedet Ikke almindelig:
General disorders and administration site conditions
Ubehag på infusionsstedet, brænden på infusionsstedet, hævelse på infusionsstedet, byld på injektionsstedet, ubehag i brystet, feber, rigor, træthed
Uncommon:
Hos et mindre antal patienter er der konstateret bivirkninger relateret til indgiftsvejen: ubehag, kløe, svie, hævelse eller steril absces ved indstikstedet.
Infusion site discomfort, infusion site burning, infusion site swelling, injection site sterile abscess, chest discomfort, fever, rigors, fatigue
Symptomer, der tyder på overfølsomhed, er set hos ca.
In a small number of patients undesirable effects have been reported which are related to the route of administration: discomfort, pruritus, burning, swelling or sterile abscess at the site of venipuncture.
3% af patienterne.
Symptoms suggestive of hypersensitivity have been noted in approximately 3% of the patients.
Sådanne symptomer er opstået under eller kort efter infusion og omfatter kløe, rødme, nældefeber/ angioødem, ubehag i brystet, takykardi, cyanose, respiratoriske symptomer samt paræstesi.
Onset of such symptoms has occurred during or shortly after infusions; these have included pruritus, flushing, urticaria/ angioedema, chest discomfort, tachycardia, cyanosis, respiratory symptoms, and paraesthesia.
Hypotension relateret til overfølsomhed er ligeledes set i sjældne tilfælde.
Hypotension associated with hypersensitivity has also been reported rarely.
Disse symptomer responderer generelt på behandling med antihistaminer og/ eller kortikosteroider.
These symptoms generally respond to treatment with antihistamines and/ or corticosteroids.
Farmakoterapeutisk klassifikation: enzymer- imiglucerase (rekombinant makrofagrettet β - glucocerebrosidase), ATC- kode:
Enzymes-Imiglucerase (recombinant macrophage targeted β - glucocerebrosidase), ATC code:
Imiglucerase (rekombinant makrofagrettet β- glucocerebrosidase) katalyserer hydrolyse af glycolipidet, glucocerebrosid, til glucose og ceramid efter den sædvanlige nedbrydningsvej for membranlipider.
Imiglucerase (recombinant macrophage targeted β -glucocerebrosidase) catalyses the hydrolysis of the glycolipid, glucocerebroside, to glucose and ceramide following the normal degradation pathway for membrane lipids.
Glucocerebrosid dannes primært ved omsætning af hæmopoietiske celler.
Glucocerebroside is primarily derived from haematopoietic cell turnover.
Gaucher' s sygdom er karakteriseret af funktionel mangel på β- glucocerebrosidasenzymaktivitet med deraf følgende akkumulering af lipidt glucocerebrosid i vævsmakrofager, der udfyldes og benævnes Gaucher- celler.
Gaucher disease is characterised by a functional deficiency in β -glucocerebrosidase enzymatic activity and the resultant accumulation of lipid glucocerebroside in tissue macrophages, which become engorged and are termed Gaucher cells.
Gaucher- celler findes typisk i lever, milt og knoglemarv samt lejlighedsvis i lunge, nyre og tarm.
Gaucher cells are typically found in liver, spleen and bone marrow and occasionally, as well, in lung, kidney and intestine.
Sekundære hæmatologiske følgetilstande omfatter svær anæmi og trombocytopeni samt den karakteristiske progressive hepatosplenomegali.
5 in addition to the characteristic progressive hepatosplenomegaly.
Mulige skeletkomplikationer
The skeletal complications are a common, and frequently the most debilitating and disabling feature of Gaucher disease.
5 omfatter knoglenekrose, osteopeni med sekundære patologiske frakturer, knogleomdannelsesfejl, osteosklerose og knoglekrise.
Possible skeletal complications are: osteonecrosis, osteopenia with secondary pathological fractures, remodeling failure, osteosclerosis and bone crises.
Læger eller sundhedspersonale opfordres til at registrere Gaucher patienter, også patienter med kroniske neuronopatiske manifestationer af sygdommen, i ” ICGG Gaucher Registry ”.
Medical or healthcare professionals are encouraged to register Gaucher patients, including those with chronic neuronopathic manifestations of the disease, in the “ ICGG Gaucher Registry”.
Formålene med ” ICGG Gaucher Registry ” er at forbedre forståelsen af Gaucher’ s sygdom og vurdere virkningen af enzymerstatningsbehandling, hvilket i sidste ende skal føre til forbedringer i den sikre og effektive brug af Cerezyme.
The objectives of the “ ICGG Gaucher Registry” are to enhance the understanding of Gaucher disease and to evaluate the effectiveness of enzyme replacement therapy, ultimately leading to improvement in the safe and efficacious use of Cerezyme.
Ved intravenøs infusion af imiglucerase i fire forskellige doseringer (7, 5, 15, 30, 60 E/ kg) i løbet af en time opnåedes stabil enzymaktivitet inden for 30 minutter.
During 1 hour intravenous infusions of 4 doses (7.5, 15, 30, 60 U/ kg) of imiglucerase, steady-state enzymatic activity was achieved by 30 minutes.
Efter infusionen faldt plasmaenzymaktiviteten hurtigt med en halveringstid på 3, 6- 10, 4 minutter.
Following infusion, plasma enzymatic activity declined rapidly with a half-life ranging from 3.6 to 10.4 minutes.
Plasma clearance var fra 9, 8 til 20, 3 ml/ min. / kg (gennemsnit ± S. D., 14, 5 ±4, 0 ml/ min. / kg).
Plasma clearance ranged from 9.8 to 20.3 ml/ min/ kg, (mean ± S. D, 14.5 ± 4.0 ml/ min/ kg).
Det vægtkorrigerede fordelingsvolumen var mellem 0, 09 og 0, 15 l/ kg (gennemsnit ± S. D., 0, 12 ±0, 02 l/ kg).
The volume of distribution corrected for weight ranged from 0.09 to 0.15 l/ kg (mean ± S. D 0.12 ± 0.02 l/ kg).
Kun en til to patienter undersøgtes imidlertid ved hvert dosisniveau og infusionshastighed.
These variables do not appear to be influenced by dose or duration of infusion, however, only 1 or 2 patients were studied at each dose level and infusion rate.
Ikke- kliniske data viser ingen speciel fare for mennesker baseret på konventionelle undersøgelser af sikkerhedsfarmakologi, toksicitet ved enkelt og gentagen dosering og genotoksicitet.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single and repeated dose toxicity, and genotoxicicty.
Fortegnelse over hjælpestoffer
6.1 List of excipients
Mannitol Natriumcitrat (til justering af pH) Citronsyremonohydrat (til justering af pH) Polysorbat 80
Mannitol Sodium citrate (to adjust pH) Citric acid monohydrate (to adjust pH) Polysorbate 80
Uforligeligheder
6.2 Incompatibilities
Opbevaringstid
6.3 Shelf life
Det skal beskyttes mod lys.
If not used immediately, in-use storage and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C - 8°C under protection from light.
Særlige opbevaringsforhold
6 6.4 Special precautions for storage
Emballage (art og indhold)
6.5 Nature and contents of container
For at opnå en tilstrækkelig mængde til nøjagtig dispensering indeholder hvert hætteglas en overfyldning på 0, 3 ml.
To provide sufficient volume to allow accurate dispensing, each vial is formulated to contain an overfill of 0.3 ml.
Pakninger:
Package sizes:
1 eller 25 hætteglas pr. karton.
1 or 25 vials per carton.
Alle emballagestørrelser markedsføres ikke nøvendigvis.
Not all package sizes may be marketed.
Pulveret til koncentrat til infusionsvæsken, opløsning skal rekonstitueres med sterilt vand, fortyndes i 0, 9% natriumkloridinfusionsvæske og derefter indgives intravenøst.
The powder for concentrate for solution for infusion has to be reconstituted with water for injections, diluted with 0.9% sodium chloride intravenous solution and then administered by intravenous infusion.
Der blandes forsigtigt, således at vandet og pulveret ikke opblandes ved stød, og således at der ikke dannes skum.
Use Aseptic Technique Reconstitution Reconstitute each vial with 5.1 ml water for injections; avoid forceful impact of water for injections on the powder and, by mixing gently, avoid foaming of the solution.
Det rekonstituerede volumen er 5, 3 ml.
The reconstituted volume is 5.3 ml.
6, 1.
The pH of the reconstituted solution is approximately 6.1.
Fortynding Den rekonstituerede opløsning indeholder 40 enheder imiglucerase pr. ml.
Dilution The reconstituted solution contains 40 units imiglucerase per ml.
Den rekonstituerede mængde tillader nøjagtig udtagelse af 5, 0 ml (svarende til 200 enheder) fra hvert hætteglas.
The reconstituted volume allows accurate withdrawal of 5.0 ml (equal to 200 units) from each vial.
Fra hvert hætteglas udtages 5, 0 ml af den rekonstituerede opløsning, og mængderne blandes.
Withdraw 5.0 ml reconstituted solution from each vial and combine the withdrawn volumes.
Bland derefter den samlede mængde med 0, 9% i. v. natriumkloridinfusionsvæske til et endeligt volumen på 100- 200 ml.
Then dilute the combined volumes with 0.9% sodium chloride intravenous solution to a total volume of 100 to 200 ml.
Mikrobiologisk sikkerhed er betinget af, at rekonstituering og opløsning er udført aseptisk.
The product diluted in 0.9% sodium chloride intravenous solution will retain chemical stability if stored up to 24 hours at 2°C and 8°C under protection from light; but microbiological safety will depend on the reconstitution and dilution having been performed aseptically.
Genzyme Europe B. V., Gooimeer 10, 1411 DD Naarden, Holland.
Genzyme Europe B. V., Gooimeer 10, 1411 DD Naarden, The Netherlands
17. november 1997 Dato for sidste fornyelse:
17 November 1997 Date of latest renewal:
Yderligere information om dette lægemiddel er tilgængelig på European Medicines Agency (EMEA) hjemmeside: http: // www. emea. europa. eu /
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Cerezyme 400 E Pulver til koncentrat til infusionsvæske, opløsning
Cerezyme 400 U Powder for concentrate for solution for infusion
Hvert hætteglas indeholder 400 enheder * imiglucerase **.
Each vial contains 400 units* of imiglucerase**.
Efter rekonstitution indeholder opløsningen 40 enheder imiglucerase pr. ml (400 E/ 10 ml).
After reconstitution, the solution contains 40 units of imiglucerase per ml (400 U/ 10 ml).
6. 6) Efter rekonstitution indeholder opløsningen 1, 24 mmol natrium (400 E/ 10 ml).
After reconstitution, the solution contains 1.24 mmol sodium (400 U/ 10 mL).
9 på 6 måneder, og fortsat brug har enten standset progression af knoglesygdommen eller resulteret i bedring af denne.
9 improvement in haematological and visceral parameters within 6 months of therapy and continued use has either stopped progression of or improved bone disease.
15% af de behandlede patienter.
Hypersensitivity Current data suggest that, during the first year of therapy, IgG antibodies to imigluceraseare formed in approximately 15% of the treated patients.
(se pkt. 4. 8).
Patients with antibody to Cerezyme (imiglucerase) have a higher risk of hypersensitivity reactions (see section 4.8).
6. 6).
10 Excipients This medicinal product contains sodium and is administered in 0.9% sodium chloride intravenous solution (see section 6.6).
Der kræves en risk/ benefit- vurdering af hver gravid Gaucher patient, eller som ønsker at blive gravid.
In pregnant Gaucher patients and those intending to become pregnant, a risk-benefit treatment assessment is required for each pregnancy.
For kvinder, der får Cerezyme, skal det overvejes at fortsætte behandling gennem hele graviditeten.
In women receiving Cerezyme treatment continuation throughout pregnancy should be considered.
Det vides ikke, om denne aktive substans udskilles i human mælk, men enzymet fordøjes sandsynligvis i barnets gastrointestinale kanal.
It is not known whether this active substance is excreted in human milk, however, the enzyme is likely to be digested in the child ’ s gastrointestinal tract
11 Nervesystemet Ikke almindelig:
11 Nervous system disorders Uncommon: