natgillin/translations-raw huggingface dataset:
Der blev også udført en yderligere undersøgelse af 15 kvindelige patienter (bærere).
A further study was also carried out in 15 female (carrier) patients.
Replagal er også blevet undersøgt hos 24 børn i alderen 6½- 18 år.
Replagal has also been studied in 24 children aged between 6 and a half and 18 years of age.
Efter 6 måneders behandling nedsatte Replagal i væsentlig grad smerterne hos patienter sammenlignet med placebobehandlede (et uvirksomt præparat) patienter.
After 6 months of therapy Replagal significantly reduced pain in patients when compared to placebo (dummy) treated patients.
Replagal reducerede den venstre ventrikelmasse med gennemsnitlig 11, 5 g, mens patienter, som modtog placebo, havde en stigning i venstre ventrikelmasse på 21, 8 g.
Replagal reduced left ventricle mass by an average of 11.5 g while patients receiving placebo had an increase in left ventricular mass of 21.8 g.
Disse resultater tyder på, at sygdomssymptomerne blev forbedret, eller at sygdommen blev stabiliseret.
These results suggest the symptoms of the disease improving or the disease becoming stable.
Virkningerne hos kvindelige patienter viste sig at være sammenlignelige med resultaterne hos mandlige patienter.
The effects in female patients were shown to be comparable to the results seen in male patients.
Børn, som modtog 6 måneders behandling med Replagal, havde ingen forøgelse af hjertets størrelse, og Gb3- niveauerne i deres blod var reduceret.
Children who received 6-month treatment with Replagal had no increase in heart, and the levels of Gb3 in their blood was reduced.
I løbet af undersøgelserne var de hyppigste bivirkninger (set hos mere end 1 patient ud af 10) forårsaget af infusionen snarere end af lægemidlet.
During the studies the most common side effects (seen in more than 1 patient in 10) are caused by the infusion rather than the medicine.
Reaktionerne var hovedsagelig kulderystelser, hovedpine, kvalme, pyreksi (feber), rødme i ansigtet og træthed, og de er sjældent alvorlige.
These reactions are mainly chills, headache, nausea, pyrexia (fever), flushing and fatigue (tiredness), and are rarely severe.
Af andre meget almindelige bivirkninger kan nævnes smerte og ubehag.
Other very common side effects were pain and discomfort.
De indberettede bivirkninger hos børn svarer til dem, der er iagttaget hos voksne patienter.
Side effects reported in children are similar to those seen in adult patients.
Den fuldstændige liste over alle indberettede bivirkninger ved Replagal fremgår af indlægssedlen.
For the full list of all side effects reported with Replagal, see the Package Leaflet.
Patienter, som modtager Replagal, kan danne antistoffer (proteiner, der dannes som reaktion på Replagal, og som kan påvirke behandlingen).
Patients who receive Replagal can develop antibodies (proteins that are produced in response to Replagal and can affect treatment).
Replagal må ikke gives til personer, der kan være overfølsomme (allergiske) over for agalsidase alfa eller et af de øvrige indholdsstoffer.
Replagal should not be used in people who may be hypersensitive (allergic) to agalsidase alfa or any of the other ingredients.
Udvalget for Humanmedicinske Lægemidler (CHMP) besluttede, at behandling med Replagal for patienter med Fabrys sygdom kunne give kliniske fordele på lang sigt.
The Committee for Medicinal products for Human Use (CHMP) decided that for patients with Fabry disease, treatment with Replagal might provide long-term clinical benefits.
CHMP besluttede, at fordelene ved Replagal er større end risiciene, og anbefalede derfor udstedelse af en markedsføringstilladelse for Replagal.
The CHMP decided that Replagal’ s benefits are greater than its risks and recommended that Replagal be given marketing authorisation.
Replagal er blevet godkendt under ” særlige omstændigheder ”, da det ikke har været muligt at indhente fyldestgørende oplysninger om lægemidlet, da sygdommen er sjælden.
Replagal has been authorised under "Exceptional Circumstances", because, as the disease is rare, it has not been possible to obtain complete information on the medicine.
Hvert år gennemgår Det Europæiske Lægemiddelagentur (EMEA) alle nye oplysninger, der måtte foreligge, og dette sammendrag ajourføres efter behov.
Every year, the European Medicines Agency (EMEA) reviews any new information that may have become available and this summary will be updated as necessary.
Hvilke oplysninger afventes der stadig for Replagal?
What information is still awaited for Replagal?
Firmaet, som fremstiller Replagal, skal udføre yderligere undersøgelser af lægemidlet og især se nærmere på resultaterne af en behandling over 5 år, andre doseringer, vedligeholdelsesdoser og undersøgelser af børn.
The company that makes Replagal will carry further studies with the medicine, looking in particular at the results of 5-year treatment, other dosages, maintenance dosages, and studies in children.
Andre oplysninger om Replagal:
Other information about Replagal:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Replagal til TKT Europe AB den 3. august 2001.
The European Commission granted a marketing authorisation valid throughout the European Union for Replagal to TKT Europe AB on 3 August 2001.
Den fuldstændige EPAR om Replagal findes her.
The full EPAR for Replagal is available here.
Særnavn Replagal
Invented name Replagal Replagal Replagal Replagal Replagal Replagal
Styrke 1 mg/ ml
Strength 1 mg/ ml 1 mg/ ml 1 mg/ ml 1 mg/ ml 1 mg/ ml 1 mg/ ml
Lægemiddelform Koncentrat til infusionsvæske, opløsning
Pharmaceutical form Concentrate for solution for injection Concentrate for solution for injection Concentrate for solution for injection Concentrate for solution for injection Concentrate for solution for injection Concentrate for solution for injection
Indgivelsesvej Intravenøs anvendelse
Route of administration Intravenous use Intravenous use Intravenous use Intravenous use Intravenous use Intravenous use
Emballage Hætteglas (glas)
Packaging Vial (glass) Vial (glass) Vial (glass) Vial (glass) Vial (glass) Vial (glass)
Pakkestørrelse 1 hætteglas
Contents 3.5 ml 3.5 ml 3.5 ml 1 ml 1 ml 1 ml
10 hætteglas
Package size 1 vial 4 vials 10 vials 1 vial 4 vials 10 vials
Replagal 1 mg/ ml koncentrat til infusionsvæske, opløsning.
Replagal 1 mg/ ml concentrate for solution for infusion.
1 ml koncentrat til infusionsvæske, opløsning, indeholder 1 mg agalsidase alfa.
1 ml of concentrate for solution for infusion contains 1 mg of agalsidase alfa.
Hvert hætteglas med 1 ml koncentrat indeholder 1 mg agalsidase alfa.
Each vial of 1 ml of concentrate contains 1 mg of agalsidase alfa.
Hvert hætteglas med 3, 5 ml koncentrat indeholder 3, 5 mg agalsidase alfa.
Each vial of 3.5 ml of concentrate contains 3.5 mg of agalsidase alfa.
Agalsidase alfa er det humane protein α- galactosidase A fremstillet ved genteknologi i en human cellelinie.
Agalsidase alfa is the human protein α -galactosidase A produced in a human cell line by genetic engineering technology.
Replagal er indiceret til langtids- enzym- substitutionsterapi i patienter med en bekræftet diagnose af Fabrys sygdom (α- galactosidase A- deficiens).
Replagal is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry Disease (α -galactosidase A deficiency).
Behandling med Replagal skal ske under vejledning af en læge med erfaring i behandling af patienter med Fabrys sygdom eller andre arvelige metaboliske sygdomme.
Replagal treatment should be supervised by a physician experienced in the management of patients with Fabry Disease or other inherited metabolic diseases.
Replagal indgives i en dosis på 0, 2 mg/ kg legemsvægt hver anden uge ved intravenøs infusion over 40 minutter.
Replagal is administered at a dose of 0.2 mg/ kg body weight every other week by intravenous infusion over 40 minutes.
For vejledning i fremstilling og indgift henvises til afsnit 6. 6.
For preparation and administration instructions, see section 6.6.
Patienter over 65 år Der er ikke gennemført studier på patienter over 65 år, og der kan ikke endnu anbefales noget doseringsregimen til disse patienter, da sikkerheden og virkningen endnu ikke er klarlagt.
Patients aged over 65 years Studies in patients over the age of 65 have not been performed and no dosage regimen can presently be recommended in these patients as safety and efficacy have not yet been established.
Patienter med leversvigt Der er ikke gennemført studier på patienter med leversvigt.
Patients with hepatic impairment No studies have been performed in patients with hepatic impairment.
Patienter med nyresvigt Det er ikke nødvendigt at foretage dosisændring hos patienter med nyresvigt.
Patients with renal impairment No dose adjustment is necessary in patients with renal impairment.
Forekomst af omfattende nyrebeskadigelse (eGFR < 60 ml/ min) kan begrænse nyrernes reaktion på enzym- substitutionsterapi.
The presence of extensive renal damage (eGFR < 60mL/ min) may limit the renal response to enzyme replacement therapy.
Der findes begrænsede data fra patienter i dialyse eller efter nyretransplantation; ingen dosisjustering anbefales.
Limited data are available in patients on dialysis or post-kidney transplantation, no dose adjustment is recommended.
Pædiatriske patienter Erfaring med børn er begrænset.
Paediatric Patients The experience in children is limited.
Der er ikke gennemført studier på børn (0- 6 år), og aktuelt kan intet doseringsregimen anbefales til patienterne, da sikkerheden og effekten ikke er fastlagt.
Studies in children (0-6 years) have not been performed and no dosage regimen can presently be recommended in the patients as safety and efficacy have not yet been established.
5. 2).
Limited clinical data in children (7-18 years) do not permit to recommend an optimal dosage regimen presently (see section 5.2).
Da ingen uventede sikkerhedsmæssige problemer blev konstateret i det 6 måneder lange studie
Because no unexpected safety issues were encountered in
2 med Replagal indgivet med 0, 2 mg/ kg i denne population, foreslås dette dosisregimen til børn i alderen 7- 18 år.
2 the 6 month study with Replagal administered at 0.2 mg/ kg in this population, this dose regimen is suggested for children between 7– 18 years of age.
Idiosynkratiske infusionsrelaterede reaktioner 13, 7% af patienter, der blev behandlet med Replagal i kliniske studier, har oplevet idiosynkratiske infusionsrelaterede reaktioner.
Idiosyncratic infusion related reactions 13.7% of patients treated with Replagal in clinical trials have experienced idiosyncratic infusion related reactions.
Procentdelen af infusionsrelaterede reaktioner var generelt lavere for kvinder end for mænd.
Overall, the percentage of infusion related reactions was significantly lower in females than males.
De mest almindelige symptomer er kulderystelser, hovedpine, kvalme, pyrexi, rødmen og træthed.
The most common symptoms have been rigors, headache, nausea, pyrexia, flushing and fatigue.
Alvorlige infusionsreaktioner er rapporteret som usædvanlige; de rapporterede symptomer inkluderer pyrexi, kulderystelser, takykardi, urticaria, kvalme/ opkastning, angioneurotisk ødem med strubeforsnævring, stridor og hævet tunge.
Serious infusion reactions have been reported uncommonly; symptoms reported include pyrexia, rigors, tachycardia, urticaria, nausea/ vomiting, angioneurotic oedema with throat tightness, stridor and swollen tongue.
Infusionsrelaterede reaktioner er generelt indtrådt inden for de første 2 – 4 måneder efter påbegyndt behandling med Replagal, om end en senere indtræden (efter 1 år) også er indberettet.
The onset of infusion related reactions has generally occurred within the first 2-4 months after initiation of treatment with Replagal although later onset (after 1 year) has been reported as well.
Hvis der indtræder milde eller moderate akutte infusionsreaktioner, skal der straks søges lægehjælp og iværksættes passende modforanstaltninger.
If mild or moderate acute infusion reactions occur, medical attention must be sought immediately and appropriate actions instituted.
Milde og forbigående effekter kræver ikke nødvendigvis medicinsk behandling eller afbrydelse af infusionen.
Mild and transient effects may not require medical treatment or discontinuation of the infusion.
Desuden kan oral eller intravenøs forbehandling med antihistaminer og/ eller kortikosteroider fra 1 til 24 timer forud for infusionen forebygge følgereaktioner i de tilfælde, hvor symptomatisk behandling var påkrævet.
In addition, oral or intravenous pre-treatment with antihistamines and/ or corticosteroids, from 1 to 24 hours prior to infusion may prevent subsequent reactions in those cases where symptomatic treatment was required.
Allergi- lignende overfølsomhedsreaktioner Som med alle intravenøse proteinholdige produkter er allergi- lignende overfølsomhedsreaktioner en mulighed.
Allergic-type hypersensitivity reactions As with any intravenous protein product, allergic-type hypersensitivity reactions are possible.
Hvis der indtræder alvorlige allergiske eller anafylaktisk- lignende reaktioner, bør indgift af Replagal øjeblikkeligt ophøre, og passende behandling iværksættes.
If severe allergic or anaphylactic-type reactions occur, the administration of Replagal should be discontinued immediately and appropriate treatment initiated.
Gældende medicinske standarder for akut behandling skal følges.
The current medical standards for emergency treatment are to be observed.
IgG- antistoffer mod proteinet Som med alle proteinholdige farmaceutiske produkter kan patienter udvikle IgG- antistoffer mod proteinet.
IgG antibodies to the protein As with all protein pharmaceutical products, patients may develop IgG antibodies to the protein.
24% af mandlige patienter behandlet med Replagal.
A low titre IgG antibody response has been observed in approximately 24% of the male patients treated with Replagal.
3- 12 måneders behandling.
These IgG antibodies appeared to develop following approximately 3-12 months of treatment.
Efter 12 til 54 måneders terapi var 17% af de Replagal- behandlede patienter stadig antistof- positive, hvorimod 7% udviste tegn på udvikling af immunologisk tolerance vurderet på baggrund af reduktionen af IgG- antistoffer med tiden.
After 12 to 54 months of therapy, 17% of Replagal treated patients were still antibody positive whereas 7% showed evidence for the development of immunologic tolerance, based on the disappearance of IgG antibodies over time.
De resterende 76% forblev hele tiden antistof- negative.
The remaining 76% remained antibody negative throughout.
Der er ikke påvist nogen IgE- antistoffer hos patienter, der var i behandling med Replagal.
No IgE antibodies have been detected in any patient receiving Replagal.
Patienter med svækket nyrefunktion Forekomsten af omfattende nyreskade kan begrænse det renale respons på enzym- substitutionsterapi, eventuelt på grund af basale, irreversible patologiske forandringer.
Patients with renal impairment The presence of extensive renal damage may limit the renal response to enzyme replacement therapy, possibly due to underlying irreversible pathological changes.
Replagal bør ikke indgives sammen med klorochin, amiodaron, benoquin eller gentamicin, da disse stoffer kan hæmme intracellulær aktivitet af α- galactosidase.
Replagal should not be co-administered with chloroquine, amiodarone, benoquin or gentamicin since these substances have the potential to inhibit intra-cellular α -galactosidase activity.
Da α- galactosidase A selv er et enzym, er det ikke nogen sandsynlig kandidat for cytokrom P450 - medieret lægemiddel- lægemiddel- interaktion.
As α -galactosidase A is itself an enzyme, it would be an unlikely candidate for cytochrome P450 mediated drug-drug interactions.
Meget begrænsede kliniske data om graviditeter, der er blevet eksponeret for Replagal (n=4), har ikke vist nogen bivirkninger på moderen og det nyfødte barn.
Very limited clinical data on pregnancies exposed to Replagal (n=4) have shown no adverse effects on the mother and newborn child.
5. 3).
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryonal/ foetal development when exposed during organogenesis (see Section 5.3).
Det vides ikke, om Replagal udskilles med brystmælk hos mennesker.
It is not known whether Replagal is excreted in human milk.
Der bør udvises forsigtighed ved ordinering til gravide eller ammende kvinder.
Caution should be exercised when prescribing to pregnant or breast-feeding women.
Replagal har ingen eller ubetydelig indflydelse på evnen til at føre motorkøretøj eller betjene maskiner.
Replagal has no or negligible influence on the ability to drive and use machines.
De mest almindelige rapporterede bivirkninger var infusionsrelaterede reaktioner, som optrådte hos 13, 7% af patienter, der blev behandlet med Replagal i kliniske studier.
The most commonly reported undesirable effects were infusion associated reactions, which occurred in 13.7% of patients treated with Replagal in clinical trials.
De fleste bivirkninger var milde til moderate.
Most undesirable effects were mild to moderate in severity.
Tabel 1 angiver bivirkninger rapporteret hos 153 patienter behandlet med Replagal i kliniske studier, herunder 21 patienter med tidligere tilfælde af nyresygdom i sidste stadie og 17 kvindelige patienter.
Table 1 lists adverse drug reactions (ADRs) reported for the 153 patients treated with Replagal in clinical trials, including 21 patients with history of endstage renal disease and 17 female patients.
Informationen angives efter systemorganklasse og hyppighed (meget almindelig > 1/ 10; almindelig > 1/ 100, < 1/ 10; usædvanlig > 1/ 1000, < 1/ 100).
Information is presented by system organ class and frequency (very common > 1/ 10; common > 1/ 100 ,< 1/10; uncommon > 1/1000 ,< 1/100).
Indenfor hver gruppe af bivirkninger med same frekvens skal bivirkningerne opstilles efter hvor alvorlige bivirkningerne er.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Samme patient kan have flere bivirkninger.
A single patient could be affected by several ADRs.
Tabel 1 Stofskiftesygdomme og ernæringsbetingede sygdomme
Table 1 Metabolism and nutrition disorders
perifert ødem
peripheral oedema
hovedpine svimmelhed, dysgeusi, neuropatisk smerte, tremor, hypersomnia, hypæstesi, paræstesi
headache dizziness, dysgeusia, neuropathic pain, tremor, hypersomnia, hypoesthesia, paraesthesia
parosmia
parosmia
rødmen hypertension
flushing hypertension
hoste, hæshed, strubeforsnævring, dyspnø, nasopharyngitis, pharyngitis, øget halsflåd, rhinorrhoea
cough, hoarseness, throat tightness, dyspnoea, nasopharyngitis, pharyngitis, throat secretion increased, rhinorrhoea
kvalme diare, opkastning, mavesmerte / - ubehag
nausea diarrhoea, vomiting, abdominal pain/ discomfort
4 Sygdomme i hud og subkutane væv
Skin and subcutaneous tissue disorders
acne, erythem, pruritus, udslæt, livedo reticularis angioneurotisk ødem, urticaria
acne, erythema, pruritus, rash, livedo reticularis angioneurotic oedema, urticaria
Sygdomme i bevægeapparatet og bindevæv
4 Musculoskeletal, connective tissue and bone disorders
ubehag i bevægeapparat, myalgi, rygsmerter, smerter i ekstremiteter, perifer hævelse, arthralgia, hævede led
musculoskeletal discomfort, myalgia, back pain, limb pain, peripheral swelling, arthralgia, joint swelling
tunghedsfornemmelse
sensation of heaviness
kulderystelser, pyrexi, smerter og ubehag, træthed forværring af træthed, feberfornemmelse, kuldefornemmelse, asteni, brystsmerter, trykken for brystet, influenza- lignende sygdom, udslæt på injektionsstedet, ildebefindende
rigors pyrexia, pain and discomfort, fatigue fatigue aggravated, feeling hot, feeling cold, asthenia, chest pain, chest tightness, influenza like illness, injection site rash, malaise
nedsat cornearefleks reduceret oxygensaturation
corneal reflex decreased oxygen saturation decreased
Se også punkt 4. 4.
See also section 4.4.
Bivirkninger, der blev indberettet for patienter med tidligere tilfælde af nyresygdom i sidste stadie, svarede til dem, der blev indberettet for den overordnede patientpopulation.
Adverse drug reactions reported in patients with history of end stage renal disease were similar to those reported in the general patient population.
Infusionsrelaterede virkninger og forværring af smerter forekom dog oftere.
However, infusion related reactions and pain exacerbation occurred more frequently.
De hyppigste var milde infusionsrelaterede virkninger, som hovedsageligt omfattede kulderystelser, pyrexi, rødmen, hovedpine, kvalme og dyspnø.
The most frequent were mild infusion-related reactions that mainly included rigors, pyrexia, flushing, headache, nausea, and dyspnoea.
Andre produkter vedrørende fordøjelseskanal og metabolisme - Enzymer.
Other alimentary tract and metabolism products - Enzymes.
A16AB03 agalsidase alfa.
A16AB03 agalsidase alfa.
Fabrys sygdom er en forstyrrelse i glycosphingolipid- deponering, som er forårsaget af en mangelfuld aktivitet af det lysosomale enzym α- galactosidase A, resulterende i akkumulation af globotriaosylceramid (også betegnet Gb3 eller CTH), glycosphingolipid- substratet for dette enzym.
Fabry Disease is a glycosphingolipid storage disorder that is caused by deficient activity of the lysosomal enzyme α -galactosidase A, resulting in accumulation of globotriaosylceramide (also referred to as Gb3 or CTH), the glycosphingolipid substrate for this enzyme.
Agalsidase alfa katalyserer hydrolysen af Gb3, idet det fjerner en terminal galaktose- rest fra molekylet.
Agalsidase alfa catalyses the hydrolysis of Gb3, cleaving a terminal galactose residue from the molecule.
Agalsidase alfa er fremstillet i en human cellelinie for at opnå en glycosyleringsprofil som hos mennesker, hvilket kan influere på optagelsen via mannose- 6 - fosfat- receptorer på overfladen af målcellerne.
Agalsidase alfa has been produced in a human cell line to provide for a human glycosylation profile that can influence uptake by mannose-6-phosphate receptors on the surface of target cells.
Sikkerheden og virkningen af Replagal blev vurderet i to randomiserede, dobbeltblindede, placebo - kontrollerede studier og åbne ekstensionsstudier i 40 patienter i alt med en diagnosticeret Fabrys sygdom baseret på klinisk og biokemisk evidens.
The safety and efficacy of Replagal was assessed in two randomised, double blind, placebo controlled studies and open label extension studies, in a total of forty patients with a diagnosis of Fabry Disease based on clinical and biochemical evidence.
Patienterne fik den anbefalede dosis af 0, 2 mg/ kg
Patients received the recommended dosage of 0.2 mg/ kg of Replagal.
Efter 6 måneders terapi var der en signifikant smertereduktion hos de Replagal- behandlede patienter sammenlignet med placebo (p=0, 021) bedømt ud fra Brief Pain Inventory (en valideret skala til måling af smerte).
After 6 months of therapy there was a significant reduction in pain in the Replagal treated patients compared with placebo (p=0.021), as measured by the Brief Pain Inventory (a validated pain measurement scale).
I efterfølgende studier af mandlige pædiatriske patienter blev en smertelindring observeret efter 9 og 12 måneders behandling med Replagal sammenlignet med baseline inden behandling.
In subsequent studies, in male paediatric patients, a reduction in pain was observed after 9 and 12 months of Replagal therapy compared to pre-treatment baseline.
12 til 18 måneders behandling med Replagal medførte en forbedring af livskvalitet (QoL) målt ved hjælp af validerede instrumenter.
5 Twelve to 18 months of treatment with Replagal resulted in improvement in quality of life (QoL), as measured by validated instruments.
Efter 6 måneders terapi stabiliserede Replagal nyrefunktionen sammenlignet med en forringelse hos placebo- behandlede patienter.
After 6 months of therapy Replagal stabilised renal function compared with a decline in placebo treated patients.
Efter 12 til 18 måneders vedligeholdelsesterapi forbedrede Replagal nyrefunktionen vurderet på grundlag af en inulin- baseret glomerulær filtreringshastighed med 8, 7 ± 3, 7 ml/ min (p=0, 030).
(p=0.030).