natgillin/translations-raw huggingface dataset:
Orale antikonceptiva Samtidig administration af 800 mg to gange dagligt og et kombineret oralt antikoceptivum (ethinylestradiol 35 μg og norethindron 1 mg) i 14 dage medførte et gennemsnitligt fald i ethinylestradiols AUC0- 24 på 22% og for norethindrons AUC0- 24 på 14%.
Oral contraceptives Co-administration of rufinamide 800 mg b. i. d. and a combined oral contraceptive (ethinyloestradiol 35 μ g and norethindrone 1 mg) for 14 days resulted in a mean decrease in the ethinyl estradiol AUC0-24 of 22% and in norethindrone AUC0-24 of 14%.
Der er ikke udført undersøgelser med andre orale eller implantable antikonceptivat.
Studies with other oral or implant contraceptives have not been conducted.
4. 4 og 4. 6).
Women of child-bearing potential using hormonal contraceptives are advised to use an additional safe and effective contraceptive method (see Section 4.4 and 4.6).
Cytokrom P450 enzymer Rufinamid metaboliseres ved hydrolyse og metaboliseres ikke i nævneværdig grad af cytokrom P450 enzymer.
Cytochrome P450 enzymes Rufinamide is metabolised by hydrolysis, and is not metabolised to any notable degree by cytochrome P450 enzymes.
5. 2).
Furthermore, rufinamide does not inhibit the activity of cytochrome P450 enzymes (see Section 5.2).
Det er således usandsynligt, at der vil forekomme interaktioner af klinisk betydning som er, medieret af rufinamids hæmning af cytokrom P450 systemet.
Thus, clinically significant interactions mediated through inhibition of cytochrome P450 system by rufinamide are unlikely to occur.
Det er blevet vist, at rufinamid inducerer cytokrom P450 enzymet CYP3A4 Rufinamid kan derfor reducere plasmakoncentrationerne af lægemidler, der metaboliseres af dette enzym.
Rufinamide has been shown to induce the cytochrome P450 enzyme CYP3A4 and may therefore reduce the plasma concentrations of drugs which are metabolised by this enzyme.
Middelaktiviteten af CYP3A, vurderet som triazolamclearance, blev forøget med 55% efter 11 dages behandling med rufinamid 400 mg 2 gange dagligt.
The mean CYP3A activity, assessed as clearance of triazolam, was increased by 55% after 11 days of treatment with rufinamide 400 mg b. i. d.
Triazolameksponeringen blev reduceret med 36%.
The exposure of triazolam was reduced by 36%.
Det kan ikke udelukkes, at rufinamid ligeledes kan nedsætte eksponeringen af lægemidler, som metaboliseres af andre enzymer, eller som transporteres af transportproteiner så som P- glycoprotein.
It may not be excluded that rufinamide may decrease the exposure also of drugs metabolized by other enzymes, or transported by transport proteins such as P-glycoprotein.
Det anbefales, at patienter, der behandles med lægemidler, som metaboliseres af CYP3A enzymsystemet, monitoreres omhyggeligt i 2 uger ved starten eller efter afslutningen af behandlingen med Inovelon, eller efter enhver markant dosisændring.
It is recommended that patients treated with drugs that are metabolised by the CYP3A enzyme system are to be carefully monitored for two weeks at the start of, or after the end of treatment with Inovelon, or after any marked change in the dose.
En dosisjustering af det samtidigt administrerede lægemiddel kan overvejes.
A dose adjustment of the concomitantly administered drug may need to be considered.
Disse anbefalinger bør ligeledes overvejes, når rufinamid anvendes samtidigt med lægemidler med et snævert terapeutisk indeks som f. eks. warfarin og digoxin.
These recommendations should also be considered when rufinamide is used concomitantly with drugs with a narrow therapeutic window such as warfarin and digoxin.
En specifik interaktionsundersøgelse hos raske forsøgspersoner afslørede ingen indflydelse af rufinamid på olanzapins, et CYP1A2 substrat, farmakokinetik ved en dosis på 400 mg 2 gange dagligt.
A specific interaction study in healthy subjects revealed no influence of rufinamide at a dose of 400 mg bid on the pharmacokinetics of olanzapine, a CYP1A2 substrate.
3% hos den almindelige befolkning.
It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population.
I hvilket omfang behandlingen og/ eller sygdommen er ansvarlig, er imidlertid ikke blevet belyst.
In the treated population, an increase in malformations has been noted with polytherapy; however, the extent to which the treatment and/ or the illness is responsible has not been elucidated.
Desuden bør effektiv antiepileptisk behandling ikke afbrydes, da forværring af sygdommen er skadelig for både moderen og fosteret.
Moreover, effective anti-epileptic therapy must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.
5. 3).
Studies in animals revealed no teratogenic effect but foetotoxicity in presence of maternal toxicity (see Section 5.3).
For rufinamids vedkommende findes der ingen kliniske data om eksponerede graviditeter.
For rufinamide, no clinical data on exposed pregnancies are available
Ligeledes bør rufinamid ikke anvendes til kvinder i den fødedygtige alder, der ikke anvender antikonception.
Taking these data into consideration, rufinamide should not be used during pregnancy unless clearly necessary and in women of childbearing age not using contraceptive measures.
5 Kvinder i den fødedygtige alder skal anvende svangerskabsforebyggende midler under behandlingen med Inovelon.
Women of childbearing potential must use contraceptive measures during treatment with Inovelon.
Lægerne skal forsøge at sikre, at der bliver anvendt passende antikonception.
Physicians should try to ensure that appropriate contraception is used, and should use clinical
Baseret på den individuelle patients kliniske situation bør de behandlende læger anvende klinisk skøn ved vurderingen af, hvorvidt perorale antikonceptionsmidler eller doserne af de perorale antikonceptionsmidlers komponenter er tilstrækkelige (se pkt.
5 judgement when assessing whether oral contraceptives, or the doses of the oral contraceptive components, are adequate based on the individual patients clinical situation (see Section 4.5).
Det vides ikke, om rufinamid udskilles i human modermælk.
Is not known if rufinamide is excreted in human breast milk.
På grund af de potentielt skadelige virkninger for det ammede barn, bør amningen undgås, så længe moderen er i behandling med rufinamid.
Due to the potential harmful effects for the breast fed infant, the lactation should be avoided during maternal treatment with rufinamide.
Inovelon kan medføre svimmelhed, somnolens og sløret syn.
Inovelon may cause dizziness, somnolence and blurred vision.
Afhængig af den individuelle følsomhed kan Inovelon have en let til kraftig indflydelse på evnen til at køre bil eller betjene maskiner.
Depending on the individual sensitivity, Inovelon may have a mild to severe influence on the ability to drive or use machines.
Patienter bør rådes til at udvise forsigtighed under aktiviteter, som kræver høj koncentration f. eks. bilkørsel eller håndtering af maskiner.
Patients must be advised to exercise caution during activities requiring a high degree of alertness, e. g., driving or operating machinery.
Det kliniske udviklingsprogram omfattede over 1. 900 patienter med forskellige typer epilepsi, som blev eksponeret for rufinamid.
The clinical development program has included over 1,900 patients, with different types of epilepsy, exposed to rufinamide.
De mest almindeligt rapporterede bivirkninger var hovedpine, svimmelhed, træthed og somnolens.
The most commonly reported adverse reactions overall were headache, dizziness, fatigue, and somnolence.
De mest almindelige bivirkninger, som blev observeret med en højere hyppighed end ved placebo hos patienter med Lennox- Gastaut’ s syndrom, var somnolens og opkastning.
The most common adverse reactions observed at a higher incidence than placebo in patients with Lennox-Gastaut syndrome were somnolence and vomiting.
Seponeringsfrekvensen ved Lennox- Gastaut’ s syndrom på grund af bivirkninger var 8, 2% for patienter, der fik Inovelon og 0% for patienter, der fik placebo.
The discontinuation rate in Lennox-Gastaut syndrome due to adverse reactions was 8.2% for patients receiving Inovelon and 0% for patients receiving placebo.
De mest almindelige bivirkninger, som medførte seponering i Inovelon- behandlingsgruppen, var udslæt og opkastning.
The most common adverse reactions resulting in discontinuation from the Inovelon treatment group were rash and vomiting.
De bivirkninger, der blev rapporteret med en hyppighed større end placebo under de dobbeltblinde forsøg med Lennox- Gastaut’ s syndrom eller i den samlede rufinamideksponerede population, er opført i nedenstående tabel i henhold til MedDRA- konventionen, systemorganklasse og hyppighed.
Adverse reactions reported with an incidence greater than placebo, during the Lennox-Gastaut syndrome double-blind studies or in the overall rufinamide-exposed population, are listed in the table below by MedDRA preferred term, system organ class and by frequency.
Hyppigheder defineres som: meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 < 1/ 10), usædvanlig (≥ 1/ 1. 000 < 1/ 100).
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 < 1/ 10), uncommon (≥ 1/ 1,000 < 1/ 100).
Systemorgan - Meget klasse Infektiøse og parasitære sygdomme
System Organ Class Infections and Infestations Immune system
Almindelig Pneumoni Influenza Nasopharyngitis Øreinfektion Sinusitis Rhinitis
Common Pneumonia Influenza Nasopharyngitis Ear infection Sinusitis Rhinitis
Forstyrrelser immunsystemet
disorders
Stofskiftesyg - domme og ernæringsbe - tingede sygdomme
Metabolism and Nutrition disorders Psychiatric disorders
Anoreksi Spiseforstyrrelser Nedsat appetit
Anorexia Eating disorder Decreased appetite Anxiety Insomnia
Systemorgan - Meget
Nervous system disorders
klasse lidelser
Somnolence* Headache Dizziness*
Almindelig Insomni
Status epilepticus* Convulsion Coordination Abnormal*
Usædvanlig
6 System Organ Class
Sjælden
Very
Sygdomme i
Common
Status epilepticus *
Common Nystagmus Psychomotor hyperactivity Tremor
nervesystemet
Uncommon
Hovedpine Svimmelhed *
Rare
Øjensygdomme
Eye Disorders
Sygdomme i det ydre og det indre øre
Ear and Labyrinth disorders
Sygdomme i åndedrætsorga - ner, brysthule og mediastinum
Respiratory, thoracic and mediastinal disorders
Epistaxis
Epistaxis
Gastrointestinal e sygdomme Sygdomme i
Gastrointestinal disorders
Øvre abdominalsmerter Obstipation Dyspepsi Diaré
Abdominal pain upper Constipation Dyspepsia Diarrhoea
lever og
Hepato-biliary
Stigning i
Hepatic enzyme
galdeveje Sygdomme i hud og
disorders Skin and subcutaneous
Udslæt *
Rash*
leverenzymer
increase
subkutane væv Sygdomme i bevægeapparate t og bindevæv
tissue disorders Musculoskeletal and connective tissue and bone disorders
Akne Rygsmerter
Acne Back pain
Lidelser i forplantningsor ganerne og brystsygdomme
Reproductive system and breast disorders
Almene lidelser Træthed og reaktioner på indgivelsesstede t
General disorders Fatigue and administration site conditions
Gangforstyrrelser *
Gait disturbance*
4. 4
Investigations Injury, poisoning *Cross refer to Section 4.4.
Vægttab Beskadigelse af hoved Kontusion
Weight decrease Head injury Contusion
Der findes intet specifikt antidot for Inovelon.
There is no specific antidote for Inovelon.
5. 2).
Treatment should be supportive and may include haemodialysis (see Section 5.2).
Gentagne doser på 7200 mg/ dagvar ikke forbundet med alvorlige tegn eller symptomer.
Multiple dosing of 7,200 mg/ day was associated with no major signs or symptoms.
Antiepileptika, carboxamidderivater; ATC- kode:
7 Pharmacotherapeutic group: anti-epileptics, carboxamide derivatives; ATC-code:
Virkningsmekanisme Rufinamid modulerer natriumkanalernes aktivitet, idet det forlænger deres inaktive tilstand.
Mechanism of action Rufinamide modulates the activity of sodium channels, prolonging their inactive state.
Rufinamid er aktivt i en række epilepsi- dyremodeller.
Rufinamide is active in a range of animal models of epilepsy.
Mandlige og kvindelige patienter (i alderen 4- 30 år) blev inkluderet, hvis de samtidigt blev behandlet med 1 til 3 antiepileptika med fast dosering.
Clinical experience Inovelon was administered in a double blind, placebo-controlled study, at doses of up to 45 mg/ kg/ day for 84 days, to 139 patients with inadequately controlled seizures associated with Lennox-Gastaut Syndrome (including both atypical absence seizures and drop attacks). Male or female patients (between 4 and 30 years of age) were included if they were being treated with 1 to 3 concomitant fixed-dose antiepileptic drugs.
28 dage under vedligeholdelsesfasen i forhold til basislinien (- 35, 8% med Inovelon vs. - 1, 6% med placebo, p=0, 0006), antallet af toniske- atonsike anfald (- 42. 9% med Inovelon vs.
A significant improvement was observed for all three primary variables: the percentage change in total seizure frequency per 28 days during the maintenance phase relative to baseline (-35.8% on Inovelon vs. – 1.6% on placebo, p= 0.0006), the number of tonic-atonic seizures (-42.9% on Inovelon vs.
2, 2% med placebo, p = 0, 0002), og sværhedsgraden af anfald ud fra den samlede evaluering udført af forældre/ værge ved afslutningen af den dobbeltblinde fase (stor forbedring eller meget stor forbedring hos 32, 2% i Inovelongruppen vs.
2.2% on placebo, p = 0.0002), and the seizure severity rating from the Global Evaluation performed by the parent/ guardian at the end of the double-blind phase (much or very much improved in 32.2% on Inovelon vs.
14, 5% i placebogruppen, p=0, 0041).
14.5% on the placebo arm, p=0.0041).
Populationsfarmakokinetisk/ farmakodynamisk modellering viste, at reduktionen af total og tonisk - atonisk anfaldsfrekvens, forbedringen af den samlede evaluering af sværhedsgraden af anfald og øgningen af sandsynligheden for reduktion af anfaldsfrekvensen var afhængig af rufinamidkoncentrationerne.
Population pharmacokinetic/ pharmacodynamic modelling demonstrated that the reduction of total and tonic-atonic seizure frequencies, the improvement of the global evaluation of seizure severity and the increase in probability of reduction of seizure frequency were dependent on rufinamide concentrations.
Absorption Den maksimale plasmakoncentration opnås ca.
Absorption Maximum plasma levels are reached approximately 6 hours after administration.
Den maksimale plasmakoncentration (Cmax) og plasma AUC for rufinamid stiger mindre end proportionalt med doserne hos både fastende og ikke fastende raske forsøgspersoner og hos patienter.
Peak concentration (Cmax) and plasma AUC of rufinamide increase less than proportionally with doses in both fasted and fed healthy subjects and in patients, probably due to dose-limited absorption behaviour.
34% og maksimal plasmakoncentration med 56%.
After single doses food increases the bioavailability (AUC) of rufinamide by approximately 34% and the peak plasma concentration by 56%.
80% af denne binding.
Distribution In in-vitro studies, only a small fraction of rufinamide (34%) was bound to human serum proteins with albumin accounting for approximately 80% of this binding.
Dette tyder på en minimal risiko for lægemiddel- lægemiddel interaktioner gennem fortrængning fra bindingsstederne ved samtidig indgift af andre lægemidler.
This indicates minimal risk of drug-drug interactions by displacement from binding sites during concomitant administration of other drugs.
8 Biotransformation Rufinamid elimineres næsten udelukkende ved metabolisme.
Biotransformation Rufinamide is almost exclusively eliminated by metabolism.
Cytokrom P450 - medieret metabolisme er meget lille.
Cytochrome P450-mediated metabolism is very minor.
Rufinamid har udvist lille eller ikke signifikant evne in- vitro til at virke som en kompetitiv eller mekanismebaseret hæmmer af følgende humane P450 enzymer:
Rufinamide has demonstrated little or no significant capacity in-vitro to act as a competitive or mechanism-based inhibitor of the following human P450 enzymes:
CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 eller CYP4A9/ 11- 2.
CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/ 5 or CYP4A9/ 11-2.
6- 10 timer hos raske forsøgspersoner og patienter med epilepsi.
Elimination The plasma elimination half-life is approximately 6-10 hours in healthy subjects and patients with epilepsy.
Ved administration to gange dagligt med 12 timers intervaller, akkumuleres rufinamid i det omfang, der forudses ud fra dets terminale halveringstid, hvilket tyder på, at rufinamids farmakokinetik er tidsuafhængig (dvs. ingen autoinduktion af metabolismen).
When given twice daily at 12-hourly intervals, rufinamide accumulates to the extent predicted by its terminal half-life, indicating that the pharmacokinetics of rufinamide are time- independent (i. e. no autoinduction of metabolism).
Rufinamid repræsenterende omkring 80% af den totale radioaktivitet, og metabolitten CGP 47292 udgjorde kun omkring 15%.
8 In a radiotracer study in three healthy volunteers, the parent compound (rufinamide) was the main radioactive component in plasma, representing about 80% of the total radioactivity, and the metabolite CGP 47292 constituting only about 15%.
Renal udskillelse var den overvejende eliminationsvej for lægemiddelrelateret stof og udgjorde 84, 7% af dosis.
Renal excretion was the predominant route of elimination for drug related material, accounting for 84.7% of the dose.
Køn Populationsfarmakokinetisk modellering har været brugt til at vurdere indflydelsen af køn på rufinamids farmakokinetik.
Pharmacokinetics in special patient groups Sex Population pharmacokinetic modelling has been used to evaluate the influence of sex on the pharmacokinetics of rufinamide.
Nedsat nyrefunktion Farmakokinetikken af en enkelt dosis på 400 mg rufinamid var uændret hos patienter med kronisk og alvorligt nedsat nyrefunktion sammenlignet med raske forsøgspersoner.
Renal impairment The pharmacokinetics of a single 400 mg dose of rufinamide were not altered in subjects with chronic and severe renal failure compared to healthy volunteers.
4. 2 og 4. 9).
However, plasma levels were reduced by approximately 30% when haemodialysis was applied after administration of rufinamide, suggesting that this may be a useful procedure in case of overdose (see Sections 4.2 and 4.9).
Nedsat leverfunktion Der er ikke udført forsøg hos patienter med nedsat leverfunktion og derfor bør Inovelon ikke administreres til patienter med alvorligt nedsat leverfunktion.
Hepatic impairment No studies have been performed in patients with hepatic impairment and therefore Inovelon should not be administered to patients with severe hepatic impairment.
Børn (2- 12 år) Børn har almindeligvis lavere rufinamidclearance end voksne og denne forskel er relateret til kropsstørrelsen.
Children (2-12 years) Children generally have lower clearance of rufinamide than adults, and this difference is related to body size.
Der er ikke udført forsøg hos nyfødte eller spædbørn og børn under 2 år.
Studies in new-born infants or infants and toddlers under 2 years of age have not been conducted.
Ældre Et farmakokinetisk forsøg hos ældre raske forsøgspersoner viste ingen signifikant forskel i farmakokinetiske parametre sammenlignet med yngre voksne.
Elderly A pharmacokinetic study in elderly healthy volunteers did not show a significant difference in pharmacokinetic parameters compared with younger adults.
Traditionelle sikkerhedsfarmakologiske forsøg afslørede ingen specielle risici ved klinisk relevante doser.
Conventional safety pharmacology studies revealed no special hazards at clinically relevant doses.
Cholestase og leverenzymstigning, anses for at være relateret til øget galdesekretion hos denne dyreart.
Toxicities observed in dogs at levels similar to human exposure at the maximum recommended dose were liver changes, including bile thrombi, cholestasis and liver enzyme elevations thought to be related to increased bile secretion in this species.
Hos rotter og aber blev der ikke fundet evidens for en associeret risiko ved toksicitetsforsøg med gentagne doser.
No evidence of an associated risk was identified in the rat and monkey repeat dose toxicity studies.
I reproduktions - og udviklingstoksicitetsforsøg sås reduktion i føtal vækst og overlevelse og nogle dødfødsler sekundært til maternel toksicitet.
In reproductive and developmental toxicity studies, there were reductions in foetal growth and survival, and some stillbirths secondary to maternal toxicity.
Inovelon var ikke teratogent hos mus, rotter eller kaniner.
Inovelon was not teratogenic in mice, rats or rabbits.
Inovelon var ikke genotoksisk og havde ikke noget karcinogent potentiale.
Rufinamide was not genotoxic and had no carcinogenic potential.
Benigne knogle neoplasmer (osteomer) og hyperostose, som blev set hos mus, blev vurderet til at være et resultat af aktiveringen af en musespecifik virus som følge af udløste fluorioner under den oxidative metabolisering af rufinamid.
Benign bone neoplasms (osteomas) and hyperostosis seen in mice were considered a result of the activation of a mouse specific virus by fluoride ions released during the oxidative metabolism of rufinamide.
Med hensyn til immunotoksisk potentiale blev små thymi og thymusinvolution set hos hunde i et studie af 13 ugers varighed med signifikant respons ved den høje dosis hos handyr.
9 Regarding the immunotoxic potential, small thymus and thymic involution were observed in dogs in a 13 week study with significant response at the high dose in male.
I det 13 uger lange studie blev en lav forekomst af knoglemarvsforandringer og lymfoide forandringer rapporteret hos hundyr ved den høje dosis.
In rats decreased cellularity of the bone marrow and thymic atrophy were observed only in the carcinogenicity study.
6. 1 Fortegnelse over hjælpestoffer Kerne:
6.1 List of excipients
Lactosemonohydrat Mikrokrystallinsk cellulose Majsstivelse Croscarmellosenatrium Hypromellose Magnesiumstearat Natriumlaurilsulfat Silica, kolloid vandfri
Lactose monohydrate Cellulose, microcrystalline Maize starch Croscarmellose sodium Hypromellose Magnesium stearate Sodium laurilsulfate Silica colloidal, anhydrous
Opadry 00F44042 [består af hypromellose, macrogol (8000), titandioxid (E171), talcum og rød jernoxid (E172)].
Opadry 00F44042 [consists of hypromellose, macrogols (8000), titanium dioxide (E171), talc and ferric oxide red (E172)].
Må ikke opbevares over 30oC
Do not store above 30ºC.
100 mg Aluminium/ aluminium blister, pakninger med 10, 30, 50, 60 og 100 filmovertrukne tabletter.
100 mg Aluminium/ aluminium blisters, packs of 10, 30, 50, 60 and 100 film-coated tablets.
10 Ikke alle pakningsstørrelser er nødvendigvis markedsført.
Not all pack sizes may be marketed.
Eisai Ltd., European Knowledge Centre, Mosquito Way, Hatfield, Herts, AL10 9SN, Storbritannien
Eisai Limited, European Knowledge Centre, Mosquito Way, Hatfield, Herts, AL10 9SN, UK
16. januar 2007
16th January 2007
200 mg Hver filmovertrukket tablet indeholder 200 mg rufinamid.
200 mg Each film-coated tablet contains 200 mg rufinamide.
40 mg lactosemonohydrat/ filmovertrukket tablet
40 mg lactose monohydrate/ film coated tablet.
200 mg Lyserød, oval, let konveks, delekærv på begge sider, præget med‘ Є262 ’ på den ene side og blank på den anden side.
200 mg Pink, ‘ ovaloid’, slightly convex, scored on both sides, embossed ‘Є 262’ on one side and blank on the other side.
Efter mindst to dage kan dosis øges med 200 mg/ dag til en anbefalet maksimaldosis på 600 mg/ dag, i henhold til klinisk respons og tolerance.
According to clinical response and tolerability, after a minimum of 2 days the dose may be increased by 200 mg/ day, to the maximum recommended dose of 600 mg/ day.
12 Anvendelse hos voksne og børn på fire år eller ældre på 30 kg eller derover Behandlingen bør indledes med en daglig dosis på 400 mg.
12 Use in adults and children four years of age or older of 30 kg or over Treatment should be initiated at a daily dose of 400 mg.
Der findes ikke tilstrækkelige data om seponering af samtidige antiepileptika, når der først er opnået kontrol over anfaldene ved tillægsbehandling med Inovelon.
There are insufficient data on the withdrawal of