natgillin/translations-raw huggingface dataset:
Hvad anvendes RILUTEK til?
What is RILUTEK used for?
RILUTEK anvendes til behandling af amyotrofisk lateral sklerose (ALS).
RILUTEK is used in patients with amyotrophic lateral sclerosis (ALS).
Sygdommen medfører muskel - svaghed, muskelsvind og lammelse.
ALS is a form of motor neurone disease where attacks of the nerve cells responsible for sending instructions to the muscles lead to weakness, muscle waste and paralysis.
RILUTEK anvendes til at forlænge patientens liv eller den tid, der går, til patienten skal have mekanisk ventilation (respirator).
RILUTEK is used to extend the patient ’ s life, or the time before they need to use mechanical ventilation.
RILUTEK bør ikke anvendes hos patienter med andre sygdomme i motorneuronerne.
RILUTEK should not be used in patients with any other form of motor neurone disease.
Hvordan anvendes RILUTEK?
How is RILUTEK used?
Behandling med RILUTEK bør kun iværksættes af en speciallæge med erfaring i behandling af syg - domme i motorneuronerne.
Treatment with RILUTEK should only be started by a specialist doctor with experience in the management of motor neurone diseases.
Til voksne og ældre patienter gives lægemidlet i en dosis på 100 mg dag - ligt (50 mg hver 12. time).
In adult and elderly patients, it is given as 100 mg a day (50 mg every 12 hours).
RILUTEK anbefales ikke til børn eller patienter med nyresygdom, og det bør ikke anvendes til patienter med leversygdom.
RILUTEK is not recommended for children or patients with kidney disease and should not be given to patients with liver disease.
Yderligere oplysninger fremgår af indlægssedlen.
For more information please see the Package Leaflet.
Hvordan virker RILUTEK?
How does RILUTEK work?
Det aktive stof i RILUTEK, riluzole, virker på nervesystemet.
The active substance in RILUTEK, riluzole, acts on the nervous system.
Det vides ikke nøjagtigt, hvordan læ - gemidlet virker ved ALS.
The exact way in which it works in ALS is not known.
Riluzole standser frigivelsen af glutamat, og dette kan medvirke til at forhindre skade på nervecellerne.
Riluzole stops the release of glutamate and this may help in preventing the nerve cells being damaged.
Hvordan blev RILUTEK undersøgt?
How has RILUTEK been studied?
Virkningen af RILUTEK blev sammenlignet med placebo (virkningsløs behandling) i tre undersøgel - ser med tilsammen 1 282 patienter.
The effectiveness of RILUTEK has been compared with that of placebo (a dummy treatment) in three studies involving a total of 1,282 patients.
I undersøgelserne blev RILUTEK givet i en dosering på 50, 100 eller 200 mg dagligt i op til 18 måneder.
Across the studies, RILUTEK was given as 50, 100 or 200 mg per day, and for up to 18 months.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 86 68 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 Hvilken fordel viser undersøgelserne, der er ved RILUTEK?
(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 What benefit has RILUTEK shown during the studies?
Den gennemsnitlige overlevelsestid for de patienter, der fik RILUTEK, var signifikant længere end for dem, der fik placebo.
The average survival time was significantly longer for patients who received RILUTEK compared with patients who received placebo.
2 måneder læn - gere end dem, der fik placebo.
Looking at the results of the three studies together, over 18 months, patients who received RILUTEK 100 mg/ day had an average survival time that was about 2 months longer than the survival time for patients who received placebo.
RILUTEK 50 mg dagligt var ikke mere effektivt end placebo, og 200 mg dagligt var ikke mere effektivt end 100 mg dagligt.
RILUTEK 50 mg/ day was no more effective than placebo and 200 mg/ day was no more effective than 100 mg/ day.
I de sene stadier af ALS virkede lægemid - let ikke bedre end placebo.
The medicine was not more effective than placebo in the late stages of ALS.
Hvilken risiko er der forbundet med RILUTEK?
What is the risk associated with RILUTEK?
De hyppigste bivirkninger af RILUTEK (som ses hos flere end 1 ud af 10 patienter) er kvalme, kraf - tesløshed og abnorme leverprøver (forhøjede leverenzymer i blodet).
The most common side effects seen with RILUTEK (in more than 1 patient in 10) are nausea (feeling sick), asthenia (weakness) and abnormal liver tests (increased in liver enzymes levels).
Den fuldstændige liste over de indberettede bivirkninger for RILUTEK fremgår af indlægssedlen.
For the full list of all side effects reported with RILUTEK, see the Package Leaflet.
RILUTEK bør ikke anvendes hos patienter, der kan være overfølsomme (allergiske) over for riluzole eller andre af indholdsstofferne.
RILUTEK should not be used in people who may be hypersensitive (allergic) to riluzole or any of the other ingredients.
RILUTEK bør ikke anvendes hos patienter med leversygdom eller unormalt højt indhold af leverenzymer i blodet.
RILUTEK should not be used in patients who have liver disease or who have abnormally high levels of liver enzymes.
RILUTEK bør desuden ikke anvendes hos patienter, der er gravide eller ammer.
RILUTEK should also not be given to women who are pregnant or breast-feeding.
Hvorfor blev RILUTEK godkendt?
Why has RILUTEK been approved?
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at fordelene ved RILUTEK op - vejer risiciene til forlængelse af overlevelsen eller af tiden, indtil mekanisk ventilation er nødvendig, for patienter med amyotrofisk lateral sklerose.
The Committee for Medicinal products for Human Use (CHMP) decided that RILUTEK’ s benefits are greater than its risks to extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis.
Udvalget konstaterede også, at der ikke er beviser for, at RILUTEK virker på den motoriske (bevægelsesmæssige) funktion, lungefunktionen, fascikulationer (muskeltrækninger), muskelstyrke eller motoriske symptomer, og at det ikke er påvist, at det virker i de sene stadier af ALS.
They noted that there is no evidence that RILUTEK exerts a therapeutic effect on motor function, lung function, fasciculations, muscle strength and motor symptoms, and that it has not been shown to be effective in the late stages of ALS.
Udvalget anbefalede udstedelse af markedsføringstilladelse for RILUTEK.
The committee recommended that RILUTEK be given marketing authorisation.
Andre oplysninger om RILUTEK:
Other information about RILUTEK:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for RILUTEK til Aventis Pharma S. A. den 10. juni 1996.
The European Commission granted a marketing authorisation valid throughout the European Union for RILUTEK to Aventis Pharma S. A. on 10 June 1996.
Denne tilladelse blev fornyet den 10. juni 2001 og den 10. juni 2006.
The marketing authorisation was renewed on 10 June 2001 and 10 June 2006.
Den fuldstændige EPAR om RILUTEK findes her.
The full EPAR for RILUTEK is available here.
Blisterpakning (uigennemsigtig PVC/ aluminium)
Blister (opaque PVC/ ALU)
En filmovertrukken tablet indeholder 50 mg riluzole
Each film-coated tablet contains 50 mg of riluzole
Tabletten er kapselformet, hvid og mærket ” RPR 202 ” på den ene side.
Film-coated tablet The tablets are capsule-shaped, white and engraved with “ RPR 202 ” on one side.
5. 1). Overlevelse er defineret som patienter, der var i live uden at være intuberet for mekanisk ventilation og uden trakeostomi.
Survival was defined as patients who were alive, not intubated for mechanical ventilation and tracheotomy-free.
Sikkerhed og effekt af RILUTEK ved andre motor- neuronsygdomme end ALS er ikke undersøgt.
Safety and efficacy of RILUTEK has only been studied in ALS.
Derfor bør RILUTEK ikke bruges til patienter med andre former af motor neuronsygdomme.
Therefore, RILUTEK should not be used in patients with any other form of motor neurone disease.
Behandling med RILUTEK bør kun iværksættes af speciallæger med erfaring i behandling af motor - neuronsygdomme.
Treatment with RILUTEK should only be initiated by specialist physicians with experience in the management of motor neurone diseases.
Anbefalet daglig dosis for voksne og ældre er 100 mg (50 mg hver 12. time).
The recommended daily dose in adults or elderly is 100 mg (50 mg every 12 hours).
RILUTEK anbefales ikke til børn, p. g. a. mangel på data vedrørende sikkerhed og virkning, af riluzole ved neurodegenerative sygdomme hos børn og unge.
RILUTEK is not recommended for use in children, due to a lack of data on the safety and efficacy of riluzole in any neurodegenerative diseases occurring in children or adolescents.
4. 4).
RILUTEK is not recommended for use in patients with impaired renal function, as studies at repeated doses have not been conducted in this population (see section 4.4).
Med udgangspunkt i de farmakokinetiske undersøgelser, er der ingen særlige anvisninger for brug af RILUTEK i denne patientgruppe.
Elderly: based on pharmacokinetic data, there are no special instructions for the use of RILUTEK in this population.
Patienter med nedsat leverfunktion:.
Patients with impaired hepatic function:
4. 3, 4. 4 og 5. 2).
(see section 4.3, section 4.4, and section 5.2).
Leversygdom eller normalværdier af transaminase på mere end 3 gange øvre normalgrænse.
Hepatic disease or baseline transaminases greater than 3 times the upper limit of normal.
Nedsat leverfunktion:
Liver impairment:
Riluzole bør gives med forsigtighed til patienter med anamnestisk patologisk leverfunktion eller til patienter med lidt forhøjede værdier af serum- transaminase (ALAT / SGTP; ASAT/ SGOT) op til 3 gange de øvre normalværdier) bilirubin og/ eller gamma- glutamyl transferase (GGT) niveauer.
Riluzole should be prescribed with care in patients with a history of abnormal liver function, or in patients with slightly elevated serum transaminases (ALT/ SGPT; AST/ SGOT up to 3 times the upper limit of the normal range (ULN)), bilirubin and/ or gamma-glutamyl transferase (GGT) levels.
4. 8).
Baseline elevations of several liver function tests (especially elevated bilirubin) should preclude the use of riluzole (see section 4.8).
På grund af risikoen for hepatitis skal serum transaminaser, inklusive ALAT, måles før og under behandling med riluzole.
Because of the risk of hepatitis, serum transaminases, including ALT, should be measured before and during therapy with riluzole.
Riluzolebehandling bør afbrydes, hvis ALAT værdierne stiger til 5 gange øvre normalværdi.
Riluzole should be discontinued if the ALT levels increase to 5 times the ULN.
Der er ingen erfaring med dosisreduktion eller re- eksposition hos patienter, som har udviklet ALAT stigning til 5 gange normalværdien.
There is no experience with dose reduction or rechallenge in patients who have developed an increase of ALT to 5 times ULN.
Fornyet indgift af riluzole til patienter i denne situation kan ikke anbefales.
Readministration of riluzole to patients in this situation cannot be recommended.
4. 8).
The report of a febrile illness should prompt physicians to check white blood cell counts and to discontinue riluzole in case of neutropenia (see section 4.8).
4. 2).
Studies at repeated doses have not been conducted in patients with impaired renal function (see section 4.2).
Der er ingen kliniske studier, der har vurderet interaktion mellem riluzole og andre lægemidler.
There have been no clinical studies to evaluate the interactions of riluzole with other medicinal products.
In vitro studier med anvendelse af human lever mikrosomale præparationer antyder, at CYP 1A2 er det principielle isoenzym involveret i den initiale oxidative metabolisme af riluzole.
In vitro studies using human liver microsomal preparations suggest that CYP 1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole.
Hæmmere af CYP 1A2 (f. eks. coffein, diclofac, diazepam, nicergolin, clomepramin, imipramin, fluvoxamin, phenacetin, theophyllin, amitriptylin, og quinoloner) kan potentielt nedsætte riluzoles eliminations- hastighed, hvorimod stoffer, der fremmer CYP 1A2 (f. eks. cigaretrygning, grillmad, rifampicin og omeprazol) kan øge eliminationshastigheden af riluzole.
Inhibitors of CYP 1A2 (e. g. caffeine, diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) could potentially decrease the rate of riluzole elimination, while inducers of CYP 1A2 (e. g. cigarette smoke, charcoal-broiled food, rifampicin and omeprazole) could increase the rate of riluzole elimination.
4. 3) under graviditeten (se pkt.
RILUTEK is contraindicated (see section 4.3) in pregnancy (see section 5.3).
Klinisk erfaring med riluzole mangler hos gravide.
Clinical experience with riluzole in pregnant women is lacking.
5. 3).
RILUTEK is contraindicated (see section 4.3) in breast-feeding women (see section 5.3).
Det vides ikke, om riluzole udskilles i human mælk.
It is not known whether riluzole is excreted in human milk.
I kliniske studier, fase III, udført på ALS patienter behandlet med rizulole, var de mest almindeligt rapporterede bivirkninger asteni, kvalme og abnorme leverfunktionstests.
In phase III clinical studies conducted in ALS patients treated with riluzole, the most commonly reported adverse reactions were asthenia, nausea and abnormal liver function tests.
De alvorligste bivirkninger skal anføres først.. Følgende benævnelser anvendes: mMeget almindelige (≥1/ 10), almindelige (≥1/ 100, < 1/ 10), ikke almindelige (≥1/ 1. 000, < 1/ 100), sjældne (≥1/ 10. 000, < 1/ 1. 000), meget sjældne (< 1/ 10. 000) og ukendte (kan ikke beregnes ud fra de tilgængelige data).
Undesirable effects ranked under headings of frequency are listed below, using the following convention: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1,000), very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
4. 4)
Blood and the lymphatic system disorders Uncommon: anaemia Not known: severe neutropenia (see section 4.4)
Anafylaktiske reaktioner, angioødem
Immune system disorders Uncommon: anaphylactoid reaction, angioedema
Hovedpine, svimmelhed, oral paræstesi og somnolens.
Nervous system disorder Common: headache, dizziness, oral paraesthesia and somnolence
Takykardi
Cardiac disorders Common: tachycardia
Pankreatitis
Gastrointestinal disorders Very common: nausea Common: diarrhoea, abdominal pain, vomiting Uncommon: pancreatitis
Abnorme leverfunktionstests *.
Hepato-biliary disorders Very common: abnormal liver function tests*.
Øget alanin aminotransferase i de første tre måneder efter påbegyndt behandling med rizulol; det var oftest forbigående og niveauet vendte tilbage til under dobbelt ULN efter 2 til 6 måneder ved fortsat behandling.
Increased alanine aminotransferase usually appeared within 3 months after the start of therapy with riluzole; they were usually transient and levels returned to below twice the ULN after 2 to 6 months while treatment was continued.
Hepatitis
In patients (n=20) from clinical studies with increases in ALT to more than 5 times the ULN, treatment was discontinued and the levels returned to less than 2 times the ULN within 2 to 4 months in most cases (see section 4.4) Not known: hepatitis
Smerte
General disorders and administration site conditions Very common: asthenia Common: pain
* Data fra studier indikerer, at asiatiske patienter kan være mere udsatte for abnorme leverfunktionstest – 3, 2% (194/ 5995) af asiatiske patienter mod 1, 8% (100/ 5641) af patienter med kaukasisk afstamning.
* study data indicate that Asian patients may be more susceptible to liver function test abnormalities - 3.2% (194/ 5995) of Asian patients and 1.8% (100/ 5641) of Caucasian patients.
Neurologiske og psykiatriske symptomer, akut toxisk encefalopati med feberdøs, koma og methæmoglobinæmi er blevet observeret i enkelte tilfælde.
Neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma, and methemoglobinemia have been observed in isolated cases.
4 I tilfælde af overdosering er behandling symptomatisk og understøttende.
In case of overdose, treatment is symptomatic and supportive.
Centralnervesystemet, øvrige lægemidler, ATC kode:
Pharmacotherapeutic group: other nervous system drugs, ATC code:
N07XX02
N07XX02.
Skønt pathogenesen ved ALS ikke er helt belyst, er der dog en formodning om, at glutaminat (den primære excitatoriske neurotransmitter i centralnervesystemet) spiller en stor rolle for celledød ved sygdommen.
Although the pathogenesis of ALS is not completely elucidated, it is suggested that glutamate (the primary excitatory neurotransmitter in the central nervous system) plays a role for cell death in the disease.
Riluzole formodes at virke ved hæmning af glutamatprocessen.
Riluzole is proposed to act by inhibiting glutamate processes.
Kliniske undersøgelser
Clinical trials
I en klinisk undersøgelse blev 155 patienter randomiseret til enten riluzole 100 mg/ dag (50 mg bid) eller placebo, og de blev fulgt i 12 til 21 måneder.
In a trial, 155 patients were randomised to riluzole 100 mg/ day (50 mg twice daily) or placebo and were followed-up for 12 to 21 months.
4. 1, var signifikant forlænget for de patienter, der havde fået riluzole sammenlignet med de patienter, som fik placebo.
Survival, as defined in the second paragraph of section 4.1, was significantly extended for patients who received riluzole as compared to patients who received placebo.
Den mediane overlevelse var 17, 7 måneder for riluzole- gruppen mod 14, 9 måneder for placebo- gruppen.
The median survival time was 17.7 months versus 14.9 months for riluzole and placebo, respectively.
Riluzole 50, 100, 200 mg/ dag eller placebo, og de blev fulgt i 18 måneder.
In a dose-ranging trial, 959 patients with ALS were randomised to one of four treatment groups: riluzole 50, 100, 200 mg/ day, or placebo and were followed-up for 18 months.
Hos patienter behandlet med riluzole 100 mg/ dag var overlevelsen signifikant forlænget sammenlignet med patienter, som fik placebo.
In patients treated with riluzole 100 mg/ day, survival was significantly higher compared to patients who received placebo.
Effekten af riluzole 50 mg/ dag var ikke signifikant forskellig fra placebo, og effekten af 200 mg/ dag var i al væsentlighed sammenlignelig med 100 mg/ dag.
The effect of riluzole 50 mg/ day was not statistically significant compared to placebo and the effect of 200 mg/ day was essentially comparable to that of 100 mg/ day.
Den mediane overlevelse nærmede sig 16, 5 måneder mod 13, 5 måneder for henholdsvis riluzole 100 mg/ dag og placebo.
The median survival time approached 16.5 months versus 13.5 months for riluzole 100 mg/ day and placebo, respectively.
I en parallel- gruppeundersøgelse designet til at bestemme effekten og sikkerheden af riluzole hos patienter i et sent stadium af sygdommen afveg overlevelse og motorisk funktion under riluzole - behandling ikke signifikant fra placebo.
In a parallel group study designed to assess the efficacy and safety of riluzole in patients at a late stage of the disease, survival time and motor function under riluzole did not differ significantly from that of placebo.
Patienterne blev fulgt i 18 måneder.
In a double-blind placebo-controlled trial designed to assess the efficacy and safety of riluzole in Japanese patients, 204 patients were randomised to riluzole 100 mg/ day (50 mg twice daily) or placebo and were followed-up for 18 months.
Tracheostomi- fri overlevelse var ikke signifikant højere hos patienter behandlet med riluzole sammenlignet med placebo.
Tracheostomy-free survival in patients treated with riluzole did not differ significantly from placebo.
Meta- analyser, der inkluderede dette studie og de ovenfor nævnte, viste en mindre tydelig effekt på overlevelse i riluzol- gruppen sammenlignet med placebo, selvom forskellene forblev statistisk signifikante.
Meta-analysis including this study and those described above showed a less striking effect on survival for riluzole as compared to placebo although the differences remained statistically significant.
Riluzoles farmakokinetik er undersøgt hos raske mandlige frivillige efter peroral enkelt - dosering af 25 til 300 mg og efter gentagen oral dosering af 25 til 100 mg to gange dagligt.
The pharmacokinetics of riluzole have been evaluated in healthy male volunteers after single oral administration of 25 to 300 mg and after multiple-dose oral administration of 25 to 100 mg bid.
Plasma niveauerne stiger lineært med dosis, og den farmakokinetiske profil er dosis- uafhængig.
Plasma levels increase linearly with the dose and the pharmacokinetic profile is dose-independent.
Ved gentagen indgift (10 dages behandling med 50 mg riluzole to gange dagligt) fordobles akkumulationen af uomdannet riluzole i plasma, og steady state nås på mindre end 5 dage.
With multiple dose administration (10 day-treatment at 50 mg riluzole bid), unchanged riluzole accumulates in plasma by about 2 fold and steady-state is reached in less than 5 days.
5 Absorption
Absorption
Riluzole absorberes hurtigt efter peroral administration med maksimal plasmakoncentration efter 60 til 90 minutter (Cmax = 173 ± 72 (SD) ng/ ml).
Riluzole is rapidly absorbed after oral administration with maximal plasma concentrations occurring within 60 to 90 minutes (Cmax = 173 ± 72 (sd) ng/ ml).
Omkring 90% absorberes og den absolutte biotilgæn - gelighed er 60 ± 18%.
About 90% of the dose is absorbed and the absolute bioavailability is 60 ± 18%.
Hastigheden og graden af absorption reduceres, når riluzole gives med fedtholdige måltider (fald i Cmax på 44%, fald af AUC på 17%).
5 The rate and extent of absorption is reduced when riluzole is administered with high-fat meals (decrease in Cmax of 44%, decrease in AUC of 17%).
Distributionsvolumen for riluzole er ca.
Riluzole is extensively distributed throughout the body and has been shown to cross the blood brain barrier.
Riluzole er ca.
The volume of distribution of riluzole is about 245 ± 69 l (3.4 l/ kg).
97% proteinbundet og bindes hovedsageligt til serumalbumin og lipoproteiner.
Riluzole is about 97% protein bound and it binds mainly to serum albumin and to lipoproteins.
Uomdannet riluzole er hovedkomponenten i plasma og metaboliseres ekstensivt af cytokrom P450 og følgende glucuronidering.
Unchanged riluzole is the main component in plasma and is extensively metabolised by cytochrome P450 and subsequent glucuronidation.
In vitro undersøgelser med humane lever præparationer viste, at cytokrom P450 1A2 er det væsentlige isoenzym i riluzole metabolismen.
In vitro studies using human liver preparations demonstrated that cytochrome P450 1A2 is the principal isoenzyme involved in the metabolism of riluzole.
Metabolitterne, som identificeres i urinen, er tre fenolderivater, et ureido- derivat og uomdannet riluzole.
The metabolites identified in urine are three phenolic derivatives, one ureido-derivative and unchanged riluzole.
Den primære metaboliske vej for riluzole er initial oxidation af cytokrom P450 1A2 fremstillende N - hydroxy- riluzole (RPR112512) riluzoles aktive hovedmetabolit.
The primary metabolic pathway for riluzole is initial oxidation by cytochrome P450 1A2 producing N- hydroxy-riluzole (RPR112512), the major active metabolite of riluzole.
Denne metabolit glucuronokonjugeres hurtigt til O - og N - glucuronider.
This metabolite is rapidly glucuronoconjugated to O- and N-glucuronides.
Riluzole udskilles hovedsagelig i urinen.
Riluzole is eliminated mainly in the urine.
90% af dosis.
The overall urinary excretion accounts for about 90% of the dose.
Kun 2% af en riluzole dosis blev genfundet uomdannet i urinen
Only 2% of a riluzole dose was recovered unchanged in the urine.