natgillin/translations-raw huggingface dataset:
Disse forbindelser påvirker det samme receptorsystem som memantin, og derfor kan bivirkninger (hovedsageligt relaterede til centralnervesystemet (CNS)) indtræffe hyppigere og være mere udtalte (se også under punkt 4. 5).
These compounds act at the same receptor system as memantine, and therefore adverse reactions (mainly central nervous system (CNS)-related) may be more frequent or more pronounced (see also section 4.5).
Visse faktorer, der kan forhøje urin- pH (se under punkt 5. 2), kan nødvendiggøre omhyggelig monitorering af patienten.
Some factors that may raise urine pH (see section 5.2 “ Elimination”) may necessitate careful monitoring of the patient.
Disse faktorer omfatter drastiske ændringer i kosten, f. eks. fra en kødholdig til en vegetarisk kost, eller fra en kraftig indtagelse af alkaliserende buffere.
These factors include drastic changes in diet, e. g. from a carnivore to a vegetarian diet, or a massive ingestion of alkalising gastric buffers.
Urin- pH kan også forhøjes ved tilstande med renal tubulær acidose (RTA) eller alvorlige urinvejsinfektioner med Proteus bacteria.
Also, urine pH may be elevated by states of renal tubulary acidosis (RTA) or severe infections of the urinary tract with Proteus bacteria.
I de fleste kliniske forsøg blev patienter med nyligt myokardieinfarkt, ubehandlet hjerteinsufficiens (NYHA klasse III- IV) eller ukontrolleret hypertension ekskluderet.
In most clinical trials, patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension were excluded.
De filmovertrukne tabletter indeholder lactosemonohydrat.
The film-coated tablets contain lactose monohydrate.
Bør ikke anvendes til patienter med arvelig galaktoseintolerans, en særlig form for hereditær laktosemangel (Lapp lactase deficiency) eller glukose/ galaktosemalabsorption.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Virkemåden antyder, at effekten af L- dopa, dopaminerge agonister og antikolinergika kan forstærkes ved samtidig behandling med NMDA- antagonister såsom memantin.
• The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.
Samtidig administration af memantin og
Concomitant
3 antispastika, dantrolen eller baklofen, kan modificere disses virkninger, og en dosisjustering kan være nødvendig. • Samtidig brug af memantin og amantadin skal undgås på grund af risikoen for farmakotoksisk psykose.
3 administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dose adjustment may be necessary. • Concomitant use of memantine and amantadine should be avoided, owing to the risk of pharmacotoxic psychosis.
Begge forbindelser er kemisk beslægtede NMDA- antagonister.
Both compounds are chemically related NMDA-antagonists.
Det samme kan gøre sig gældende for ketamin og dextromethorfan (se også under punkt 4. 4).
The same may be true for ketamine and dextromethorphan (see also section 4.4).
Der findes en publiceret kasuistik, der også viser en mulig risiko ved kombination af memantin og fenytoin. • Andre aktive stoffer såsom cimetidin, ranitidin, procainamid, quinidin, quinin og nikotin, der bruger samme renale kationiske transportsystem som amantadin, kan muligvis også have interaktion med memantin, hvilket kan medføre en risiko for forhøjede plasmaniveauer. • Der er mulighed for en reduktion i serumkoncentrationen af hydrochlorothiazid (HCT), når memantin administreres sammen med HCT eller sammen med kombinationspræparater med HCT. • Efter markedsføringen er der rapporteret enkeltstående tilfælde af stigninger i international normalized ratio (INR) hos patienter i samtidig behandling med warfarin.
There is one published case report on a possible risk also for the combination of memantine and phenytoin. • Other active substances such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine that use the same renal cationic transport system as amantadine may also possibly interact with memantine leading to a potential risk of increased plasma levels. • There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when memantine is co-administered with HCT or any combination with HCT. • In post-marketing experience isolated cases with international normalized ratio (INR) increases have been reported in patients concomitantly treated with warfarin.
Der sås ingen relevante interaktioner mellem de aktive stoffer i memantin og glyburid/ metformin henholdsvist donepezil i enkeltdosis farmakokinetiske (PK) - studier hos yngre, raske forsøgspersoner.
In single-dose pharmacokinetic (PK) studies in young healthy subjects no relevant active substance- active substance interaction of memantine with glyburide/ metformin or donepezil was observed.
Dyrestudier antyder en potentiel mulighed for intrauterin væksthæmning ved eksponeringsniveauer, der er identiske med eller lidt højere end human eksponering (se under punkt 5. 3).
Animal studies indicate a potential for reducing intrauterine growth at exposure levels, which are identical or slightly higher than at human exposure (see section 5.3).
Moderat til svær Alzheimers sygdom nedsætter normalt evnen til at føre et motorkøretøj eller betjene maskiner.
Moderate to severe Alzheimer’ s disease usually causes impairment of driving performance and compromises the ability to use machinery.
Derudover har Axura mindre til moderat indflydelse på evnen til at føre motorkøretøj eller betjene en maskine, hvorfor ambulante patienter skal gøres opmærksom på at være særligt forsigtige.
Furthermore, Axura has minor to moderate influence on the ability to drive and use machines such that outpatients should be warned to take special care.
I kliniske forsøg med 1. 784 patienter i behandling med Axura for mild til svær demens og med 1. 595 patienter i placebobehandling adskilte den generelle incidensrate for biverkninger med Axura sig ikke fra placebobehandlingen, og bivirkningerne var som regel milde til moderate.
In clinical trials in mild to severe dementia, involving 1,784 patients treated with Axura and 1,595 patients treated with placebo, the overall incidence rate of adverse reactions with Axura did not differ from those with placebo; the adverse reactions were usually mild to moderate in severity.
Følgende bivirkninger i nedenstående tabel er indrapporteret i forbindelse med kliniske forsøg med Axura og efter markedsføring.
The most frequently occurring adverse reactions with a higher incidence in the Axura group than in the placebo group were dizziness (6.3% vs 5.6%, respectively), headache (5.2% vs 3.9%), constipation (4.6% vs 2.6%), somnolence (3.4% vs 2.2%) and hypertension (4.1% vs 2.8%).
Inden for hver enkelt frekvensgruppe er bivirkningerne opstillet efter, hvor alvorlige de er.
The following Adverse Reactions listed in the Table below have been accumulated in clinical studies with Axura and since its introduction in the market.
Meget almindelig (≥1/ 10), almindelig (≥1/ 100 til < 1/ 10), ikke almindelig (≥1/ 1. 000 til < 1/ 100), sjælden (≥1/ 10. 000 til < 1/ 1. 000), meget sjælden (< 1/ 10. 000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Adverse reactions are ranked according to system organ class, 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).
Hjertelidelser Lidelser i nervesystemet
Cardiac failure
Ikke almindelig Almindelig Ikke almindelig Meget sjælden
disorders
Hjertesvigt Svimmelhed Unormal gang Krampeanfald
Uncommon
Lidelser i mave- tarmkanalen
Gait abnormal
Almindelig Ikke almindelig Ikke kendt
Gastrointestinal disorders
Forstoppelse Opkastning Betændelse i bugspytkirtlen (pancreatitis) 2
Infections and infestations
Infektioner og parasitære sygdomme Vaskulære sygdomme
Fungal infections
Ikke almindelig Almindelig Ikke almindelig
Vascular disorders
Svampeinfektioner Hypertension Blodpropper (Venetrombose / tromboembolisme)
Hypertension
Almene symptomer og reaktioner på administrationsstedet
Venous thrombosis/ thromboembolism
Almindelig
General disorders and administration site conditions
Hovedpine
Uncommon
Ikke almindelig
Psychiatric disorders
Træthed
Uncommon
Psykiske forstyrrelser 1
Confusion
Almindelig Ikke almindelig Ikke almindelig Ikke kendt
Hallucinations1
Sløvhed (søvntrang) Forvirring Hallucinationer1 Psykotiske reaktioner2
Psychotic reactions2
Hallucinationer er hovedsageligt observeret hos patienter med svær Alzheimers sygdom.
1 Hallucinations have mainly been observed in patients with severe Alzheimer´s disease.
Alzheimers sygdom er blevet sat i forbindelse med depression, selvmordsforestilling og selvmord.
2 Isolated cases reported in post-marketing experience Alzheimer ’ s disease has been associated with depression, suicidal ideation and suicide.
200 mg og 105 mg/ dag i 3 dage) har været forbundet med symptomer på enten træthed, svaghed og/ eller diarré eller ingen symptomer.
Relative large overdoses (200 mg and 105 mg/ day for 3 days, respectively) have been associated with either only symptoms of tiredness, weakness and/ or diarrhoea or no symptoms.
I tilfælde af overdosering med doser under 140 mg eller ukendt dosis har patienterne haft symptomer fra centralnervesystemet (forvirring, døsighed, sløvhed (søvntrang), svimmelhed, agitation, aggression, hallucinationer og gangforstyrrelser) og/ eller fra mave- tarmkanalen (opkastning og diarré).
In the overdose cases below 140 mg or unknown dose the patients revealed symptoms from central nervous system (confusion, drowsiness, somnolence, vertigo, agitation, aggression, hallucination, and gait disturbance) and/ or gastrointestinal origin (vomiting and diarrhoea).
I det alvorligste tilfælde af overdosering overlevede patienten en peroral indtagelse af i alt 2000 mg memantin med virkninger på centralnervesystemet (koma i 10 dage, og senere hen diplopi og agitation).
In the most extreme case of overdose, the patient survived the oral intake of a total of 2000 mg memantine with effects on the central nervous system (coma for 10 days, and later diplopia and agitation).
I et andet tilfælde med stor overdosis overlevede patienten også og kom sig.
5 In another case of a large overdose, the patient also survived and recovered.
Patienten havde symptomer fra centralnervesystemet såsom rastløshed, psykose, visuelle hallucinationer, pro- konvulsiv aktivitet, søvntrang, sløvhed og bevidstløshed.
The patient experienced central nervous system symptoms such as restlessness, psychosis, visual hallucinations, proconvulsiveness, somnolence, stupor, and unconsciousness.
Der bør anvendes passende standardprocedurer for at fjerne det aktive stof, f. eks. ventrikeltømning, medicinsk kul (afbrydelse af potentiel enterohepatisk recirkulation), surgøring af urinen og forceret diurese.
Standard clinical procedures to remove active substance material, e. g. gastric lavage, carbo medicinalis (interruption of potential entero-hepatic recirculation), acidification of urine, forced diuresis should be used as appropriate.
Andet antidemenspræparat, ATC- kode:
Other Anti-dementia drugs, ATC code:
Ved neurodegenerativ demens er der meget der tyder på, at malfunktion af den glutamaterge neurotransmission, i særdeleshed ved NMDA- receptorer, både medvirker til, at symptomerne kommer til udtryk, og at sygdommen forværres.
There is increasing evidence that malfunctioning of glutamatergic neurotransmission, in particular at NMDA-receptors, contributes to both expression of symptoms and disease progression in neurodegenerative dementia.
Memantin er en ikke- kompetitiv, spændingsafhængig NMDA- receptorantagonist med moderat affinitet.
Memantine is a voltage-dependent, moderate-affinity uncompetitive NMDA-receptor antagonist.
I en pivotal monoterapiundersøgelse med en patientpopulation, der led af moderat til svær Alzheimers sygdom (med en samlet Mini mental state examination (MMSE) - score ved baseline på 3 – 14), indgik i alt 252 ambulante patienter.
A pivotal monotherapy study in a population of patients suffering from moderate to severe Alzheimer’ s disease (mini mental state examination (MMSE) total scores at baseline of 3 - 14) included a total of 252 outpatients.
Undersøgelsen viste gavnlig effekt af memantinbehandlingen sammenlignet med placebo over en behandlingsperiode på 6 måneder (” observed cases analysis ” for Clinician' s interview based impression of change (CIBIC- plus): p=0, 025; Alzheimer´s disease cooperative study – activities of daily living (ADCS- ADLsev): p=0, 003; SIB: p=0, 002).
The study showed beneficial effects of memantine treatment in comparison to placebo at 6 months (observed cases analysis for the clinician´s interview based impression of change (CIBIC-plus): p=0.025; Alzheimer´s disease cooperative study – activities of daily living (ADCS-ADLsev): p=0.003; severe impairment battery (SIB): p=0.002).
I en pivotal monoterapiundersøgelse med memantin til behandling af mild til moderat Alzheimers sygdom (med en samlet MMSE- score ved baseline på 10 – 22) indgik 403 patienter.
A pivotal monotherapy study of memantine in the treatment of mild to moderate Alzheimer’ s disease (MMSE total scores at baseline of 10 to 22) included 403 patients.
Hos patienterne behandlet med memantin sås en statistisk signifikant bedre effekt end hos patienterne behandlet med placebo på de primære effektmål:
Memantine-treated patients showed a statistically significantly better effect than placebo-treated patients on the primary endpoints:
Alzheimer´s disease assessment scale (ADAS- cog) (p=0, 003) og CIBIC- plus (p=0, 004) i uge 24 (Last observation carried forward (LOCF)).
Alzheimer´s disease assessment scale (ADAS-cog) (p=0.003) and CIBIC-plus (p=0.004) at week 24 last observation carried forward (LOCF).
I en anden monoterapiundersøgelse med mild til moderat Alzheimers sygdom blev i alt 470 patienter randomiseret (samlet MMSE- score ved baseline 11 – 23).
In another monotherapy study in mild to moderate Alzheimer’ s disease a total of 470 patients (MMSE total scores at baseline of 11-23) were randomised.
En metaanalyse af patienter med moderat til svær Alzheimers sygdom (med en samlet MMSE- score < 20) fra de seks fase III, placebokontrollerede undersøgelser af 6 måneders varighed (inkl. monoterapiundersøgelser og undersøgelser med patienter behandlet med fastdosis acetylkolinesterasehæmmere) viste, at memantin havde en statistisk signifikant effekt på de kognitive, globale og funktionelle domæner.
A meta-analysis of patients with moderate to severe Alzheimer’ s disease (MMSE total scores < 20) from the six phase III, placebo-controlled, 6-month studies (including monotherapy studies and studies with patients on a stable dose of acetylcholinesterase inhibitors) showed that there was a statistically significant effect in favour of memantine treatment for the cognitive, global, and functional domains.
11%, p < 0, 0001).
11%, p < 0.0001).
Absorption:
6 Absorption:
100%. tmax er mellem 3 og 8 timer.
Memantine has an absolute bioavailability of approximately 100%. tmax is between 3 and 8 hours.
Daglige doser på 20 mg giver steady- state- plasmakoncentrationer for memantin på mellem 70 og 150 ng/ ml (0, 5 - 1 µmol) med store interindividuelle variationer.
Daily doses of 20 mg lead to steady-state plasma concentrations of memantine ranging from 70 to 150 ng/ ml (0.5 - 1 µmol) with large interindividual variations.
Ved indgivelse af daglige doser på 5 til 30 mg udregnedes en gennemsnitlig (cerebrospinalvæske) CSF/ serumværdi på 0, 52.
When daily doses of 5 to 30 mg were administered, a mean cerebrospinal fluid (CSF)/ serum ratio of 0.52 was calculated.
10 l/ kg.
The volume of distribution is around 10 l/ kg.
80% af det cirkulerende memantin- relaterede materiale til stede som modersubstans.
In man, about 80% of the circulating memantine-related material is present as the parent compound.
Humane hovedmetabolitter er N- 3, 5- dimethyl- gludantan, den isomeriske blanding af 4 - og 6- hydroxy- memantin og 1- nitroso- 3, 5- dimethyl- adamantan.
Main human metabolites are N-3,5-dimethyl-gludantan, the isomeric mixture of 4- and 6-hydroxy-memantine, and 1-nitroso-3,5-dimethyl-adamantane.
Ingen af disse metabolitter udviser NMDA- antagonistisk aktivitet.
None of these metabolites exhibit NMDA-antagonistic activity.
In vitro er der ikke fundet nogen cytokrom P450 - metabolisme.
No cytochrome P 450 catalysed metabolism has been detected in vitro.
6 I et studie med peroral indgivelse af 14C- memantin blev gennemsnitligt 84% af dosis udskilt inden for 20 dage, mere end 99% blev udskilt via nyrerne.
In a study using orally administered 14C-memantine, a mean of 84% of the dose was recovered within 20 days, more than 99% being excreted renally.
Hos frivillige forsøgspersoner med normal nyrefunktion er den totale clearance (Cltot) 170 ml/ min/ 1, 73 m2, og en del af den totale renale clearance opnås ved tubulær sekretion.
In volunteers with normal kidney function, total clearance (Cltot) amounts to 170 ml/ min/ 1.73 m² and part of total renal clearance is achieved by tubular secretion.
Den renale eliminationsrate for memantin kan, under alkaliske urinforhold, reduceres med en faktor på 7 til 9 (se under punkt 4. 4).
The renal elimination rate of memantine under alkaline urine conditions may be reduced by a factor of 7 to 9 (see section 4.4).
Alkalisering af urin kan skyldes drastiske ændringer i kosten, f. eks. fra en kødholdig til en vegetarisk kost eller fra en kraftig indtagelse af alkaliserende buffere.
Alkalisation of urine may result from drastic changes in diet, e. g. from a carnivore to a vegetarian diet, or from the massive ingestion of alkalising gastric buffers.
Dosislinearitet:
Linearity:
Farmakokinetiske/ farmakodynamiske forhold:
Pharmacokinetic/ pharmacodynamic relationship:
Ved en dosis af memantin på 20 mg pr. dag svarer CSF- niveauerne til ki- værdien (ki = hæmningsfaktor) for memantin, som er 0, 5 µmol i den humane frontale cortex.
At a dose of memantine of 20 mg per day the CSF levels match the ki-value (ki = inhibition constant) of memantine, which is 0.5 µmol in human frontal cortex.
I kortidsstudier på rotter har memantin ligesom andre NMDA- antagonister kun induceret neuronal vakuolisering og nekrose (Olney- læsioner) efter doser, der medfører meget høje maksimale serumkoncentrationer.
In short term studies in rats memantine like other NMDA-antagonists have induced neuronal vacuolisation and necrosis (Olney lesions) only after doses leading to very high peak serum concentrations.
Da virkningerne hverken er blevet observeret i langtidsstudier hos gnavere eller hos ikke- gnavere, er den kliniske relevans af disse observationer ukendt.
As the effects have neither been observed in long term studies in rodents nor in non-rodents, the clinical relevance of these findings is unknown.
Lactosemonohydrat Mikrokrystallinsk cellulose Kolloidt vandfrit silika Talkum Magnesiumstearat
Lactose monohydrate Microcrystalline cellulose Colloidal anhydrous silica Talc Magnesium stearate
7 Tabletovertræk:
Tablet coat:
Metakrylsyre – etylakrylat- kopolymer (1: 1) Natriumlaurylsulfat Polysorbat 80 Talkum Triacetin Simetikon- emulsion
Methacrylic acid - ethyl acrylate copolymer (1:1) Sodium lauryl sulphate Polysorbate 80 Talc Triacetin Simethicone emulsion
Blisterpakninger med enten 7, 10, 14 eller 20 tabletter pr. blisterstrip (Alu/ PP)..
Blister packs containing either 7, 10, 14 or 20 tablets per blister strip (Alu/ PP).
Fås i pakningsstørrelser på 14, 28, 30, 42, 50, 56, 98, 100, 112, 980 (10 x 98) eller 1. 000 (20 x 50) tabletter.
Pack sizes of 14, 28, 30, 42, 50, 56, 98, 100, 112, 980 (10 x 98) or 1000 (20 x 50) tablets are presented.
100 D- 60318 Frankfurt/ Main Tyskland
100 D-60318 Frankfurt/ Main Germany
8 Dato for første markedsføringstilladelse:
Date of first authorisation:
17/ 05/ 2002 Dato for seneste genregistrering:
17/ 05/ 2002 Date of latest renewal:
MM/ ÅÅÅÅ
MM/ YYYY
Detaljerede oplysninger om dette produkt fås på websitet for European Medicines Agency (EMEA) http: // www. emea. europa. eu
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Axura 10 mg/ g orale dråber, opløsning.
Axura 10 mg/ g oral drops, solution.
1 g opløsning indeholder 10 mg memantinhydrochlorid (svarende til 8, 31 mg memantin).
1 g of solution contains 10 mg of memantine hydrochloride equivalent to 8.31 mg memantine.
Èn dråbe opløsning svarer til 0, 5 mg memantinhydrochlorid
One drop of solution is equivalent to 0.5 mg memantine hydrochloride.
4. 4.
1 g of solution contains 100 mg sorbitol E420 and 0.5 mg potassium, see section 4.4.
Orale dråber, opløsning.
Oral drops, solution.
Dråberne kan indtages uafhængigt af måltider.
The drops can be taken with or without food.
Patienten bør indtage 10 dråber (5 mg) dagligt i 7 dage.
The patient should take 10 drops (5 mg) per day for 7 days.
Patienten bør indtage 20 dråber (10 mg) dagligt i 7 dage.
The patient should take 20 drops (10 mg) per day for 7 days.
Patienten bør indtage 30 dråber (15 mg) dagligt i 7 dage.
The patient should take 30 drops (15 mg) per day for 7 days.
Patienten bør indtage 40 dråber (20 mg) én gang dagligt i 7 dage.
The patient should take 40 drops (20 mg) once a day.
10 Den anbefalede vedligeholdelsesdosis er 20 mg dagligt.
10 Maintenance dose The recommended maintenance dose is 20 mg per day.
På baggrund af de kliniske studier er den anbefalede dosis til patienter over 65 år 20 mg pr. dag (40 dråber en gang dagligt), som beskrevet ovenfor.
On the basis of the clinical studies, the recommended dose for patients over the age of 65 years is 20 mg per day (40 drops once a day) as described above.
Samtidig brug af andre N- metyl- D- aspartat( NMDA) - antagonister såsom amantadin, ketamin eller dextromethorfan bør undgås.
Concomitant use of other N-methyl-D-aspartate (NMDA)-antagonists such as amantadine, ketamine or dextromethorphan should be avoided.
Disse forbindelser påvirker det samme receptorsystem som memantin, og derfor kan bivirkninger (hovedsageligt relaterede til centralnervesystemet (CNS)) indtræffe hyppigere og være mere udtalte (se også under punkt 4. 5).
These compounds act at the same receptor system as memantine, and therefore adverse reactions (mainly central nervous system (CNS)-related may be more frequent or more pronounced (see also section 4.5).
Orale dråber indeholder sorbitol.
The oral drops contain sorbitol.
Samtidig administration af memantin og antispastika, dantrolen eller baklofen, kan modificere disses virkninger, og en dosisjustering kan være nødvendig.
Concomitant
11 • Samtidig brug af memantin og amantadin skal undgås på grund af risikoen for farmakotoksisk psykose.
11 administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dose adjustment may be necessary. • Concomitant use of memantine and amantadine should be avoided, owing to the risk of pharmacotoxic psychosis.