natgillin/translations-raw huggingface dataset:
For de primære farmakokinetiske parametre, dvs. AUC og Cmax, blev der påvist bioækvivalens af 150 mg tabletten, idet 90 % sikkerhedsintervallet lå inden for de foreskrevne grænser 80-125 %.
Bioequivalence was demonstrated with regard to the primary pharmacokinetic parameters, i.e. AUC and Cmax, in the study with the 150 mg tablet, as the 90% CIs were within the required 80-125% limits.
Da produktresuméet for referencelægemidlet ikke indeholdt anbefalinger om fødeindtagelse og ikke omtalte en effekt af fødeindtagelse, indeholdt ansøgningen om markedsføringstilladelse for Merisone to bioækvivalensundersøgelser, der blev udført med filmovertrukne tabletter med tolperison, 50 og 150 mg, begge med 52 forsøgspersoner under fastende betingelser.
Since the summary of product characteristics (SmPC) of the reference medicinal product did not make any recommendations regarding food and did not mention a food effect, the MAA that was submitted for Merisone included two bioequivalence studies with 50 and 150 mg tolperisone film-coated tablets conducted under fasting conditions with 52 volunteers each.
Skønt den indsigende medlemsstat anså resultaterne af bioækvivalensundersøgelserne for at være på grænsen, fremførte ansøgeren, at designet af den anden bioækvivalensundersøgelse var en gentagelse, og at undersøgelsen viste, at tolperison er omfattet af stor variation - den intraindividuelle variabilitet af Cmax for referencelægemidlet var 46,99 %.
Although the results of the bioequivalence studies were considered to be borderline by the objecting CMS, the applicant argued that the second bioequivalence study was a replicate design study where it was shown that tolperisone is a highly variable drug - the within-subject variability of the reference medicinal product Cmax was 46.99%.
Da der ikke er evidens for, at virkningen af fødeindtagelse afhænger af formuleringen, konkluderede et flertal i CHMP, at bioækvivalensundersøgelser i fastende tilstand (som anses for den mest følsomme betingelse) i dette tilfælde er tilstrækkelig evidens som grundlag for en konklusion om bioækvivalens i både fastende og postprandial tilstand.
As there is no evidence that the food-effect is formulation dependent, the majority of the CHMP concluded that the bioequivalence studies conducted in the fasting state, which is considered to be the most sensitive condition, would give sufficient evidence to conclude on the bioequivalence in both the fasting and fed states in this particular case.
Den indsigende medlemsstat fandt derfor, at de to bioækvivalensundersøgelser, der var forelagt med 50 og 150 mg tolperison tabletter i fastende tilstand, var utilstrækkelige, og at der burde påvises bioækvivalens under postprandiale betingelser.
Therefore the objecting member state was of the view that the two bioequivalence submitted with the 50 and 150mg tolperisone tablets under fasting conditions were not sufficient, and that bioequivalence should be demonstrated under fed conditions.
Ansøgeren fremhævede, at på tidspunktet for udførelsen af bioækvivalensundersøgelserne indeholdt produktresumeet for referencelægemidlet ingen anbefalinger om fødeindtagelse eller omtale af betydningen heraf.
The applicant highlighted that, at the time the bioequivalence studies were performed, the summary of product characteristics (SmPC) of the reference medicinal product did not make any recommendations regarding food and did not mention that the food effect was significant.
Under hensyn til al den fremførte evidens og argumentation konstaterede et flertal af udvalgets medlemmer, at der var påvist fastende bioækvivalens for tolperison, som er højopløseligt og højpermeabelt og udviser stor intraindividuel variation.
Taking into account all the evidence and arguments presented, the majority of the CHMP noted that that bioequivalence had been demonstrated in the fasting state for tolperisone, which is highly soluble and highly permeable active substance, demonstrating high within-subject variability.
I undersøgelsen med 50 mgtabletten blev der ikke påvist bioækvivalens, da den øvre grænse for Cmax var 125,49 %, dvs. uden for den foreskrevne værdi.
In the study with the 50 mg tablet, bioequivalence was not demonstrated as the upper limit of the Cmax was outside the upper band, i.e.
CHMP bemærkede også, at hjælpestofferne mannitol og betain, som fandtes i produktet omfattet af indbringelsen, men ikke i referencelægemidlet, var uden indflydelse på bioækvivalensen af disse produkter ved fastende indtagelse.
The CHMP also noted that the excipients mannitol and betaine found in the product subject to the referral but not in the reference medicinal product, had no effect on the bioequivalence of these products in fasting state.
CHMP bemærkede at hjælpestofferne mannitol og betain, der fandtes i produktet omfattet af indbringelsen, men ikke i referencelægemidlet, var uden indflydelse på den fastende bioækvivalens af disse produkter.
The CHMP noted that the excipients mannitol and betaine found in the product subject to the referral but not in the reference medicinal product, had no effect on the bioequivalence of these products in fasting state.
Derudover blev arbejdsgruppen vedrørende farmakokinetik (PKWP) anmodet om at udtale sig om en eventuel videnskabelig begrundelse for at forvente bioækvivalens i enten fastende eller postprandial tilstand af tolperison (der klassificeres som et stærkt variabelt lægemiddel, da den intraindividuelle variabilitet af Cmax for referencelægemidlet var 46,99 %).
The Pharmacokinetics Working Party (PKWP) was also consulted to seek their view on whether there is any scientific reasoning that tolperisone (classified as a highly variable drug as the within-subject variability of the Cmax of the reference medicinal product was 46.99%) may have the option of showing bioequivalence in either the fasted or fed state.
På grundlag af de forelagte bioækvivalensundersøgelse fandt CHMP's medlemmer derfor, at tabletterne med tolperison, 50 og 150 mg ved fastende indtagelse er bioækvivalente med referencelægemidlet Mydeton, tabletter, 50 og 150 mg (Gedeon Richter Plc).
Therefore based on the results of the submitted bioequivalence studies, the CHMP members agreed that Merisone 50 and 150 mg tablets are bioequivalent to the reference medicinal product Mydeton 50 and 150-mg tablets (Gedeon Richter Plc) under fasting conditions.
• udvalget fandt, at de forelagte bioækvivalensundersøgelse viste, at Merisone, tabletter, 50 og 150 mg, under fastende betingelser var bioækvivalente med referencelægemidlet Mydeton, tabletter, 50 og 150 mg,
• The Committee was of the view that results of the submitted bioequivalence studies showed that Merisone 50 and 150 mg tablets was bioequivalent to the reference medicinal product Mydeton 50 and 150-mg tablets under fasting conditions;
Andre medlemmer af PKWP var den opfattelse, at en postprandial undersøgelse kun var overflødig, hvis virkningen af fødeindtagelse udelukkende var hepatisk, hvilket der imidlertid ikke fandtes at være tilstrækkeligt grundlag for.
Other PKWP members were of the view that a fed study would not have been required only if the effects of food were known to be solely hepatic, which however was considered to be insufficiently supported, and since the food effect for tolperisone was considered to be significantly high, a study in a fed state should have been performed.
Dette fremgik af produktresuméet for referencelægemidlet på ansøgningstidspunktet for den markedsføringstilladelse, som denne indbringelse vedrører1.
However more recently the effect of food on the bioavailability of tolperisone has been established to be significant and was reflected accordingly in the SmPC of the reference medicinal product at the time of submission of the MAA subject to this referral1.
Fortæl det til din læge, hvis du bliver gravid under behandlingen.
Tell your doctor if you become pregnant during treatment.
Hyppighederne defineres som:
The frequencies are defined as:
• Behandlingen starter normalt med en lav dosis.
Treatment usually starts with a low dose.
Proteinbinding af rivastigmin er ca. 40 %.
Protein binding of rivastigmine is approximately 40 %.
Din læge vil fortælle dig, hvilken dosis Rivastigmin Teva du skal tage.
Your doctor will tell you what dose of Rivastigmine Teva to take.
Gennemsnitsændring ved 24 uger ± SD
Mean change at 24 weeks ± SD
Øvrige indholdsstoffer er:
The other ingredients are:
• Din læge vil gradvist øge din dosis afhængigt af, hvordan du reagerer på behandlingen.
Your doctor will slowly increase your dose depending on how you respond to the treatment.
Indehaveren af markedsføringstilladelsen skal sikre, at pharmacovigilance-systemetunder modul 1.8.1. i ansøgningen om markedsføringstilladelsen, er i orden og fungerer inden og mens produktet er på markedet.
The MAH must ensure that the system of pharmacovigilance presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Bivirkningerne i tabel 1 er ordnet ifølge MedDRA-systemorganklasser og frekvenskategorier.
Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency category.
Sidste udførte observation (Last Observation Carried Forward)
Last Observation Carried Forward
De fleste tilfælde af tilfældig overdosering har ikke været forbundet med kliniske tegn eller symptomer, og næsten alle de pågældende patienter fortsatte behandlingen med rivastigmin.
Most cases of accidental overdose have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment.
Patienter med klinisk signifikant respons (%) Behandlingsintention (Intent to Treat)
Patients with Clinically Significant Response (%) Intent to Treat
• Du skal tage medicinen hver dag for at få gavn af den.
To benefit from your medicine, take it every day.
Brug ikke Rivastigmin Teva efter den udløbsdato, der står på pakningen.
Do not use Rivastigmine Teva after the expiry date that is stated on the carton.
Disse hændelser førte til seponering af rivastigmin i nogle tilfælde (f.eks. seponering grundet tremor 1,7 % på rivastigmin versus 0 % på placebo).
These events led to the discontinuation of rivastigmine in some cases (e.g. discontinuations due to tremor 1.7 % on rivastigmine vs 0 % on placebo).
I tilfælde af alvorlig opkastning, der er associeret med rivastigmin-behandling, skal der foretages passende dosisjustering som anbefalet i afsnit 4.2.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made.
ADAS-Cog Placebo Patienter uden visuelle hallucinationer
ADAS-Cog Placebo Patients without visual hallucinations
Hvis du finder ud af, at du har glemt at tage en dosis Rivastigmin Teva, skal du blot vente og tage næste dosis på det sædvanlige tidspunkt.
If you find you have forgotten to take your dose of Rivastigmine Teva, wait and take the next dose at the usual time.
Rivastigmin Teva må ikke anvendes til børn og unge (under 18 år).
The use of Rivastigmine Teva in children and adolescents (age below 18 years) is not recommended.
Rivastigmin Teva kan imidlertid anvendes hos denne patientpopulation, men det er nødvendigt at følge patienterne tæt.
However, Rivastigmine Teva may be used in this patient population and close monitoring is necessary.
Yderligere information om dette lægemiddel er tilgængelig på Det europæiske Lægemiddelagenturs (EMAs) hjemmeside http://www.ema.europa.eu
Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu
2 Middeldata vist for belejlighed, kategorisk analyse, der blev udført ved brug af van Elteren-test ITT: Intent-To-Treat; RDO: Retrieved Drop Outs; LOCF: Last Observation Carried Forward.
2 Mean data shown for convenience, categorical analysis performed using van Elteren test ITT: Intent-To-Treat; RDO: Retrieved Drop Outs; LOCF: Last Observation Carried Forward
Aktivt stof er rivastigmin.
The active substance is rivastigmine
Hvis du ikke har taget Rivastigmin Teva i flere dage, må du ikke tage den næste dosis, før du har talt med din læge.
If you have not taken Rivastigmine Teva for several days, do not take the next dose until you have talked to your doctor.
Mindst 4-pointsforbedring af ADAS-Cog med ingen forværring af CIBIC-Plus og PDS *p<0,05, **p<0,01, ***p<0,001
At least 4 points improvement on ADAS-Cog with no worsening on CIBIC-Plus and PDS *p<0.05, **p<0.01, ***p<0.001
Disse omfatter ADAS-Cog (en præstationsbaseret måling af kognition), CIBICPlus (en omfattende global vurdering af patienten, der dannes af den behandlende læge med input fra den omsorgsgivende person) og PDS (den omsorgsgivende persons vurdering af dagligdagsaktiviteter, som indbefatter personlig hygiejne, fødeindtagelse, påklædning, husføring som indkøb, opretholdelse af evner så som at orientere sig i forhold til omgivelserne og involvere sig i økonomiske anliggender og så videre).
These include the ADAS-Cog (a performance based measure of cognition), the CIBIC-Plus (a comprehensive global assessment of the patient by the physician incorporating caregiver input), and the PDS (a caregiver-rated assessment of the activities of daily living including personal hygiene, feeding, dressing, household chores such as shopping, retention of ability to orient oneself to surroundings as well as involvement in activities relating to finances, etc.).
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TEVA UK Ltd Brampton Road, Hampden Park, Eastbourne, East Sussex, BN22 9AG United Kingdom
Effekten er blevet fastslået ved hjælp af to uafhængige skalaer, som blev vurderet ved regelmæssige intervaller i løbet af en 6-måneders behandlingsperiode, som vist i tabel 5 nedenfor: ADAS-Cog, en måling af kognition og den globale måling ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change).
Efficacy has been established by the use of two independent scales which were assessed at regular intervals during a 6-month treatment period as shown in Table 5 below: the ADAS-Cog, a measure of cognition, and the global measure ADCS-CGIC (Alzheimer's Disease Cooperative StudyClinician's Global Impression of Change).
Denne metabolit viser in vitro minimal hæmning af acetylkolinesterase (<10 %).
In vitro, this metabolite shows minimal inhibition of acetylcholinesterase (<10 %).
PDS: mindst 10 % forbedring
PDS: improvement of at least
De mest almindeligt rapporterede bivirkninger er gastrointestinale, inklusive kvalme (38 %) og opkastning (23 %), særligt under dosistitrering.
The most commonly reported adverse reactions are gastrointestinal, including nausea (38 %) and vomiting (23 %), especially during titration.
28 hårde kapsler 50 x 1 hårde kapsler 56 hårde kapsler 112 hårde kapsler
28 hard capsules 50 x 1 hard capsules 56 hard capsules 112 hard capsules
• Tag Rivastigmin Teva to gange om dagen (morgen og aften) sammen med mad.
Take Rivastigmine Teva twice a day, in the morning and evening, with food.
Rivastigmin skal indtages to gange dagligt sammen med henholdsvis morgen- og aftenmåltid.
Rivastigmine should be administered twice a day, with morning and evening meals.
Andre bivirkninger, der er set med Rivasigmin Teva depotplaster, og som kan forekomme ved brug af hårde kapsler:
Other side effects seen with Rivastigmine transdermal patches and which may occur with hard capsules:
Absolut biotilgængelighed efter en 3 mg dosis er ca. 36 % ± 13 %.
Absolute bioavailability after a 3 mg dose is about 36 % ± 13 %.
Anvendelsen af dette lægemiddel er kontraindiceret hos patienter med - overfølsomhed over for det aktive stof, andre carbamatderivater eller over for et eller flere af
The use of this medicinal product is contraindicated in patients with - hypersensitivity to the active substance, other carbamate derivatives or to any of the excipients
Det krydser let blodhjernebarrieren og har et tilsyneladende fordelingsvolumen på 1,8-2,7 l/kg.
It readily crosses the blood brain barrier and has an apparent volume of distribution in the range of 1.8 - 2.7 l/kg.
På grund af kolinesterasehæmmeres kendte vagotoniske effekt på hjerterytmen kan der også forekomme bradykardi og/eller synkope.
Due to the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/or syncope may also occur.
ADAS-Cog: mindst 4pointsforbedring
ADAS-Cog: improvement of at least 4 points
Hos patienter med Alzheimers sygdom var rivastigmins hæmning af AChE i CSF afhængig af dosis op til 6 mg, der blev indgivet to gange dagligt, som var den højeste dosis, som blev testet.
In patients with Alzheimer's disease, inhibition of AChE in CSF by rivastigmine was dose-dependent up to 6 mg given twice daily, the highest dose tested.
Efter indgift af 14C-rivastigmin var renal udskillelse hurtig og nærmest fuldstændig (>90 %) inden for 24 timer.
Following administration of 14C-rivastigmine, renal elimination was rapid and essentially complete (>90 %) within 24 hours.
Planen for PSUR-indsendelse for Rivastigmin hårde kapsler skal følge planen for PSUR-indsendelse for referencemedicinalproduktet.
The PSUR submission schedule for Rivastigmine TEVA hard capsules should follow PSURs submission schedule for the reference medicinal product.
Kliniske undersøgelser af demens, der er associeret med Parkinsons sygdom Effekten af rivastigmin ved demens, der er associeret med Parkinsons sygdom, er demonstreret i et 24-ugers multicenter, dobbelt-blindt, placebo-kontrolleret hovedstudie og dets 24-ugers open-label forlængelsesfase.
Clinical studies in dementia associated with Parkinson's disease The efficacy of rivastigmine in dementia associated with Parkinson's disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase.
Hos raske, unge mænd sænker en peroral dosis på 3 mg aktiviteten af acetylkolinesterase (AChE) i CSF med ca. 40 % inden for den første 1,5 time efter indgift.
In healthy young men, an oral 3 mg dose decreases acetylcholinesterase (AChE) activity in CSF by approximately 40 % within the first 1.5 hours after administration.
EFFEKTIV ANVENDELSE AF LÆGEMIDLET Ikke relevant.
EFFECTIVE USE OF THE MEDICINAL PRODUCT Not applicable
Resultater fra in vitro og dyreundersøgelser viser, at cytokrom-P450-isoenzymer kun i ringe grad er involveret i rivastigmin-metabolisering.
Based on evidence from in vitro and animal studies the major cytochrome P450 isoenzymes are minimally involved in rivastigmine metabolism.
Indgift af rivastigmin sammen med føde forsinker optagelsen (tmax) med 90 min, sænker Cmax og øger AUC med ca. 30 %.
Administration of rivastigmine with food delays absorption (tmax) by 90 min and lowers Cmax and increases AUC by approximately 30 %.
• Svær forvirring.
• Severe confusion
Langsom hjerterytme og besvimelsesanfald kan ligeledes forekomme.
Slow heart beat and fainting may also occur.
I de fleste tilfælde vil bivirkningerne gradvist forsvinde, når kroppen vænner sig til medicinen.
Usually, the side effects slowly go away as your body gets used to the medicine.
• Leversygdomme (gulfarvet hud, gulfarvning af det hvide i øjnene, unormalt mørk urin eller uforklarlig kvalme, opkastning, træthed og appetitløshed)
• Liver disorders (yellow skin, yellowing of the whites of eyes, abnormal darkening of the urine or unexplained nausea, vomiting, tiredness and loss of appetite)
Der foreligger ikke kliniske data om eksponering for rivastigmin under graviditet.
For rivastigmine no clinical data on exposed pregnancies are available.
Rivastigmin Teva anvendes til behandling af hukommelsesproblemer hos patienter med Alzheimers sygdom.
Rivastigmine Teva is used for the treatment of memory disorders in patients with Alzheimer's disease.
Tag altid Rivastigmin Teva nøjagtigt efter lægens anvisning.
Always take Rivastigmine Teva exactly as your doctor has told you.
Rivastigmin var ikke mutagen i et standardbatteri af in vitro- og in vivo-test, på nær i en kromosonal abberationstest i humane perifere lymfocytter ved en dosis på 104 gange den maksimale kliniske relevante.
Rivastigmine was not mutagenic in a standard battery of in vitro and in vivo tests, except in a chromosomal aberration test in human peripheral lymphocytes at a dose 104 times the maximum clinical exposure.
4.9 Overdosering Symptomer
4.9 Overdose Symptoms
Rivastigmins hæmning af butyrylkolinesterase-aktivitet i CSF hos 14 patienter med Alzheimer var sammenlignelig med hæmningen af AChE.
Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by rivastigmine was similar to that of AChE.
Hvis du har glemt at tage Rivastigmin Teva
If you forget to take Rivastigmine Teva
Det er bedst at undgå at tage Rivastigmin Teva under graviditet, medmindre det er strengt nødvendigt.
It is preferable to avoid the use of Rivastigmine Teva during pregnancy, unless clearly necessary.
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Hvis denne dosis tåles godt efter mindst to ugers behandling, kan dosis øges til 3 mg to gange dagligt.
If the dose is well tolerated after a minimum of two weeks of treatment, the dose may be increased to 3 mg twice a day.
Kapselskal - titandioxid (E171), gelatine og farve til prægning Black S-1-17822/S-1-17823 (shellac glasur-45 % i ethanol indeholdende sort jernoxid, N-butylalkohol, isopropylalkohol, propylenalkohol og ammoniumhydroxid).
Capsule shell - titanium dioxide (E171), gelatin and ink used for imprinting Black S-1-17822/S-117823 (shellac glaze-45% in ethanol containing iron oxide black, N-butyl alcohol, isopropyl alcohol, propylene alcohol and ammonium hydroxide).
Hvis et eller flere af disse symptomer gælder for dig, kan det være nødvendigt, at din læge følger dig tæt, så længe du tager denne medicin.
If any of these apply to you, your doctor may need to monitor you more closely while you are on this medicine.
Det anvendes også til behandling af demens hos patienter med Parkinsons sygdom.
It is also used for the treatment of dementia in patients with Parkinson's disease.
Under 1 % af den indgivne dosis udskilles med fæces.
Less than 1 % of the administered dose is excreted in the faeces.
Rivastigmin Teva kan påvirke antikolinerg medicin (medicin, der bruges mod mavekramper og Parkinsons sygdom eller til at forebygge transportsyge).
Rivastigmine Teva might interfere with anticholinergic medicines (medicines used to relieve stomach cramps or spasms, to treat Parkinson's disease or to prevent travel sickness).
Der blev ikke observeret effekt på fertiliteten eller fosterudviklingen hos rotter og kaniner undtaget doser, der medførte maternal toksicitet.
No effects on fertility or embryofoetal development were observed in rats and rabbits, except at doses related to maternal toxicity.
Når eksponeringen for rivastigmin og dets metabolitter blev sat i relation til arealet af legemsoverfladen var det omtrent ækvivalent til den maksimalt anbefalede humane daglige dosis på 12 mg; ved sammenligning med maksimal human dosis blev der dog opnået en seksdobling af dosis hos dyr.
When normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately equivalent to the maximum recommended human dose of 12 mg/day; however, when compared to the maximum human dose, a multiple of approximately 6-fold was achieved in animals.
Rivastigmin Teva kan som al anden medicin give bivirkninger, men ikke alle får bivirkninger.
Like all medicines, Rivastigmine Teva can cause side effects, although not everybody gets them.
Der har været et tilfælde af indtagelse af 46 mg; efter traditionel behandling kom patienten sig fuldstændigt inden for 24 timer.
Ingestion of 46 mg occurred in one case; following conservative management the patient fully recovered within 24 hours.