natgillin/translations-raw huggingface dataset:
Der kan indtræffe bivirkninger, der er forbundet med forlængelse af PR- intervallet (f. eks. atrioventrikulær blok, synkope, bradykardi).
Adverse reactions associated with PR interval prolongation (e. g. atrioventricular block, syncope, bradycardia) may occur.
Hos epilepsipatienter er incidensraten af første grads AV- blok ikke almindelig: henholdsvis 0, 7%, 0%, 0, 5% og 0% for lacosamid 200 mg, 400 mg, 600 mg eller placebo.
In epilepsy patients the incidence rate of reported first degree AV Block is uncommon, 0.7%, 0%, 0.5% and 0% for lacosamide 200 mg, 400 mg, 600 mg or placebo, respectively.
Der blev ikke observeret nogen AV- blok af anden grad eller højere hos patienter behandlet med lacosamid.
No second or higher degree AV Block was seen in lacosamide treated patients.
Incidensraten for synkope er ikke almindelig, og der var ingen forskel mellem de epilepsipatienter, der fik lacosamid (0, 1%), og de epilepsipatienter, der fik placebo (0, 3%).
The incidence rate for syncope is uncommon and did not differ between lacosamide treated epilepsy patients (0.1%) and placebo treated epilepsy patients (0.3%).
Der er begrænset klinisk erfaring med overdosis af lacosamid hos mennesker.
There is limited clinical experience with lacosamide overdose in humans.
De kliniske symptomer (svimmelhed og kvalme) efter daglige doser på 1200 mg var hovedsagelig relateret til centralnervesystemet og mave- tarmkanalen og kunne løses med dosisjusteringer.
Clinical symptoms (dizziness and nausea) following doses of 1200 mg/ day were mainly related to the central nervous system and the gastrointestinal system and resolved with dose adjustments.
Den højest rapporterede overdosis i det kliniske udviklingsprogram for lacosamid var 12 g, der blev
The highest reported overdose in the clinical development program for lacosamide was 12 g taken in conjunction with toxic doses of multiple other antiepileptic drugs.
5 taget sammen med toksiske doser af flere andre antiepileptika.
The subject was initially comatose and then fully recovered without permanent sequelae.
5. 2).
Treatment of lacosamide overdose should include general supportive measures and may include haemodialysis if necessary (see section 5.2).
Farmakoterapeutisk gruppe: øvrige antiepileptika, ATC- kode:
Pharmacotherapeutic group: other antiepileptics, ATC code:
N03AX18 Det aktive stof, lacosamid (R- 2- acetamid- N- benzyl- 3- methoxypropionamid), er en funktionaliseret aminosyre.
N03AX18 The active substance, lacosamide (R-2-acetamido-N-benzyl-3-methoxypropionamide) is a functionalised amino acid.
Virkningsmekanisme Den præcise mekanisme, hvormed lacosamid udøver en antiepileptisk effekt hos mennesker, mangler stadig at blive fuldt ud belyst.
Mechanism of action The precise mechanism by which lacosamide exerts its antiepileptic effect in humans remains to be fully elucidated.
To observationer, der kan have relevans for de observerede terapeutiske effekter, er:
Two observations that may be of relevance for the observed therapeutic effects are:
In vitro- elektrofysiologiske studier har vist, at lacosamid selektivt øger den langsomme inaktivering af de spændingsstyrede natriumkanaler, der medfører en stabilisering af de hyperexcitable neuronale membraner.
In vitro electrophysiological studies have shown that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes.
Lacosamid binder endvidere til 'collapsin response mediator protein- 2 (CRMP- 2)', et fosfoprotein, der primært udtrykkes i nervesystemet og er involveret i neuronal differentiering og kontrol af udvækst af aksoner.
Further, lacosamide binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein which is mainly expressed in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth.
Farmakodynamiske effekter Lacosamid beskyttede mod anfald i en lang række dyremodeller med fokale og primært generaliserede anfald og forsinkede udviklingen af 'kindling'.
Pharmacodynamic effects Lacosamide protected against seizures in a broad range of animal models of partial and primary generalized seizures and delayed kindling development.
I ikke- kliniske forsøg viste lacosamid i kombination med levetiracetam, carbamazepin, phenytoin, valproat, lamotrigin, topiramat eller gabapentin synergistiske eller additive antikonvulsive effekter.
In non-clinical experiments lacosamide in combination with levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, topiramate or gabapentin showed synergistic or additive anticonvulsant effects.
Klinisk erfaring Effekten af Vimpat som tillægsbehandling ved de anbefalede doser (200 mg daglig, 400 mg daglig) blev dokumenteret i 3 randomiserede, placebo- kontrollerede, multicenter- kliniske forsøg med en vedligeholdelsesperiode på 12 uger.
Clinical experience The efficacy of Vimpat as adjunctive therapy at recommended doses (200 mg/ day, 400 mg/ day) was established in 3 multicenter, randomized, placebo-controlled clinical trials with a 12-week maintenance period.
Vimpat 600 mg viste sig også at være effektiv i kontrollerede forsøg med tillægsbehandling, selvom effekten var den sammesom ved 400 mg/ dag og patienterne ofte tålte denne dosis dårligere på grund af bivirkninger relateret til centralnervesystemet og mave - tarmkanalen.
Vimpat 600 mg/ day was also shown to be effective in controlled adjunctive therapy trials, although the efficacy was similar to 400 mg/ day and patients were less likely to tolerate this dose because of CNS- and gastrointestinal-related adverse reactions.
Derfor bør en daglig dosis på 600 mg ikke anvendes.
Thus, the 600 mg/ day dose is not recommended.
Den anbefalede maksimale dosis er 400 mg/ dag.
The maximum recommended dose is 400 mg/ day.
Disse forsøg, der omfattede 1308 patienter, som i gennemsnit havde haft fokale anfald i 23 år, blev designet til at vurdere lacosamids sikkerhed og virkning, når det blev givet samtidig med 1- 3 antiepileptika til patienter med ukontrollerede fokale anfald med eller uden sekundær generalisering.
These trials, involving 1308 patients with a history of an average of 23 years of partial-onset seizures, were designed to evaluate the efficacy and safety of lacosamide when administered concomitantly with 1-3 antiepileptic drugs in patients with uncontrolled partial-onset seizures with or without secondary generalisation.
Samlet var omfanget af personer med en 50% reduktion i hyppigheden af anfald 23%, 34% og 40% for placebo, lacosamid 200 mg/ dag og lacosamid 400 mg/ dag.
Overall the proportion of subjects with a 50% reduction in seizure frequency was 23%, 34%, and 40% for placebo, lacosamide 200 mg/ day and lacosamide 400 mg/ day.
Absorption Lacosamid absorberes hurtigt og fuldstændigt efter peroral indgift.
Absorption Lacosamide is rapidly and completely absorbed after oral administration.
100%.
The oral bioavailability of lacosamide tablets is approximately 100%.
0, 5 til 4 timer efter dosisindtagelsen.
Following oral administration, the plasma concentration of unchanged lacosamide increases rapidly and reaches Cmax about 0.5 to 4 hours post-dose.
Vimpat- tabletter og oral syrup er bioækvivalente.
Vimpat tablets and oral syrup are bioequivalent.
Mad har ingen effekt på graden og omfanget af absorption.
Food does not affect the rate and extent of absorption.
0, 6 l/ kg.
Distribution The volume of distribution is approximately 0.6 L/ kg.
Lacosamid er bundet mindre end 15% til plasmaproteiner.
Lacosamide is less than 15% bound to plasma proteins.
6 Metabolisme 95% af dosis udskilles i urinen som lacosamid og metabolitter.
Metabolism 95% of the dose is excreted in the urine as drug and metabolites.
40% af dosis) og dets O- desmethyl- metabolit mindre end 30%.
The major compounds excreted in urine are unchanged lacosamide (approximately 40% of the dose) and its O-desmethyl metabolite less than 30%.
20% i urinen, men kunne kun påvises i små mængder (0- 2%) i plasma hos visse patienter.
A polar fraction proposed to be serine derivatives accounted for approximately 20% in urine, but was detected only in small amounts (0-2%) in human plasma of some subjects.
Små mængder (0, 5- 2%) af øvrige metabolitter blev fundet i urinen.
Small amounts (0.5-2%) of additional metabolites were found in the urine.
CYP2C19 er primært ansvarlig for dannelsen af O- desmethyl- metabolitten.
However, no
Der blev imidlertid ikke observeret nogen klinisk relevant forskel i eksponeringen for lacosamid, når man sammenlignede med farmakokinetikken hos patienter med hurtig metabolisering (med et funktionelt CYP2C19 enzym) og patienter med langsom metabolisering (uden et funktionelt CYP2C19 enzym).
6 clinically relevant difference in lacosamide exposure was observed comparing its pharmacokinetics in extensive metabolisers (EMs, with a functional CYP2C19) and poor metabolisers (PMs, lacking a functional CYP2C19).
Desuden viste et interaktionsforsøg med omeprazol (CYP2C19- hæmmer) ingen klinisk relevante ændringer i plasmakoncentrationerne af lacosamid, hvilket kunne tyde på, at denne eliminationsvej har mindre betydning.
Furthermore an interaction trial with omeprazole (CYP2C19-inhibitor) demonstrated no clinically relevant changes in lacosamide plasma concentrations indicating that the importance of this pathway is minor.
Plasmakoncentrationen af O- desmethyl- lacosamid svarer til ca.
No other enzymes have been identified to be involved in the metabolism of lacosamide.
15% af lacosamidkoncentrationen i plasma.
The plasma concentration of O-desmethyl-lacosamide is approximately 15% of the concentration of lacosamide in plasma.
Eliminering Lacosamid elimineres først og fremmest fra det systemiske kredsløb ved udskillelse gennem nyrerne og ved biotransformation.
Elimination Lacosamide is primarily eliminated from the systemic circulation by renal excretion and biotransformation.
95% af den indgivne radioaktivitet genfundet i urinen og under 0, 5% i fæces.
After oral and intravenous administration of radiolabeled lacosamide, approximately 95% of radioactivity administered was recovered in the urine and less than 0.5% in the feces.
13 timer.
The elimination half-life of the unchanged drug is approximately 13 hours.
Farmakokinetikken er proportional med dosis og konstant over tid med lav intra - og interindividuel variation.
The pharmacokinetics is dose-proportional and constant over time, with low intra- and inter-subject variability.
Med dosering to gange daglig nås steady- state plasmakoncentrationerne efter 3 dage.
Following twice daily dosing, steady state plasma concentrations are achieved after a 3 day period.
2.
The plasma concentration increases with an accumulation factor of approximately 2.
Farmakokinetikken i særlige patientgrupper Køn Kliniske forsøg tyder på, at køn ikke har nogen klinisk signifikant betydning for lacosamids plasmakoncentration.
Pharmacokinetics in special patient groups Gender Clinical trials indicate that gender does not have a clinically significant influence on the plasma concentrations of lacosamide.
30% hos patienter med mild til moderat nedsat nyrefunktion og 60% hos patienter med alvorligt nedsat nyrefunktion samt hæmodialyse - krævende patienter med nyresygdom i slutstadiet, mens cmax var upåvirket.
Renal impairment The AUC of lacosamide was increased by approximately 30% in mildly and moderately and 60% in severely renal impaired patients and patients with endstage renal disease requiring hemodialysis compared to healthy subjects, whereas cmax was unaffected.
50%.
Following a 4-hour haemodialysis treatment, AUC of lacosamide is reduced by approximately 50%.
4. 2).
Therefore dosage supplementation following haemodialysis is recommended (see section 4.2).
Eksponeringen af O- desmethyl- metabolitten var forhøjet adskillige gange hos patienter med moderat og alvorlig nedsat nyrefunktion.
The exposure of the O-desmethyl metabolite was several-fold increased in patients with moderate and severe renal impairment.
Ved fravær af hæmodialyse hos patienter med nyresygdom i slutstadiet var niveauerne forhøjet og steg uafbrudt under 24- timers prøvetagningen.
In absence of haemodialysis in patients with endstage renal disease, the levels were increased and continuously rising during the 24-hour sampling.
50% højere AUCnorm).
Hepatic impairment Subjects with moderate hepatic impairment (Child-Pugh B) showed higher plasma concentrations of lacosamide (approximately 50% higher AUCnorm).
Det blev vurderet, at den nedsatte ikke- renale clearance hos patienterne, der indgik i undersøgelsen, ville give en stigning på 20% i lacosamids AUC.
The decrease in non-renal clearance in the patients of the study was estimated to give a 20% increase in the AUC of lacosamide.
4. 2).
The pharmacokinetics of lacosamide has not been evaluated in severe hepatic impairment (see section 4.2).
30 og 50% forøget sammenlignet med AUC hos raske unge mænd.
Elderly (over 65 years of age) In a study in elderly men and women including 4 patients > 75 years of age, AUC was about 30 and 50% increased compared to young men, respectively.
Forskellen i kropsvægt er henholdsvis 26 og 23%.
The body weight normalized difference is 26 and 23%, respectively.
Der blev også observeret forøget foranderlighed i
An increased variability in exposure was also observed.
4. 2).
A general dose reduction is not considered to be necessary unless indicated due to reduced renal function (see section 4.2).
I toksicitetsstudierne var de opnåede lacosamid plasmakoncentrationer lig med eller kun en anelse højere end dem, man observerede hos patienter, hvorfor marginen for human eksponering er lille eller ikke- eksisterende.
In the toxicity studies, the plasma concentrations of lacosamide obtained were similar or only marginally higher than those observed in patients, which leaves low or non-existing margins to human
Et farmakologisk sikkerhedsstudie med intravenøs indgift af lacosamid i bedøvede hunde viste kortvarige stigninger i PR- interval og QRS- kompleks og fald i blodtrykket, hvilket højst sandsynligt skyldes kardiodepression.
7 exposure A safety pharmacology study with intravenous administration of lacosamide in anesthetized dogs showed transient increases in PR interval and QRS complex duration and decreases in blood pressure most likely due to a cardiodepressant action.
Disse kortvarige ændringer begyndte i samme koncentrationsområde som efter den maksimale anbefalede kliniske dosering. Der blev observeret nedsat atrial - og ventrikulær ledningsevne, atrioventrikulær blok og atrioventrikulær dissociation i bedøvede hunde og Cynomolgus- aber ved intravenøse doser på 15- 60 mg/ kg.
These transient changes started in the same concentration range as after maximum recommended clinical dosing.
I toksicitetsstudier med gentagne doser blev der observeret lette reversible leverforandringer i rotter, disse leverforandringer begyndte ved ca.
In anesthetized dogs and Cynomolgus monkeys, at intravenous doses of 15-60 mg/ kg, slowing of atrial and ventricular conductivity, atrioventricular block and atrioventricular dissociation were seen.
3 gange den kliniske eksponering.
In the repeated dose toxicity studies, mild reversible liver changes were observed in rats starting at about 3 times the clinical exposure.
I reproduktionsstudier og udviklings- toksicitetsstudier med gnavere og kaniner blev der ikke observeret teratogene virkninger, men derimod en stigning i antallet af dødfødte unger og mortalitet lige omkring fødslen samt et lidt lavere antal levende unger pr. kuld og noget lavere kropsvægt hos ungerne ved maternelt toksiske doser i rotter svarende til systemiske eksponeringsniveauer, der er identiske med den forventede kliniske eksponering.
In reproductive and developmental toxicity studies in rodents and rabbits, no teratogenic effects but an increase in numbers of stillborn pups and pup deaths in the peripartum period, and slightly reduced live litter sizes and pup body weights were observed at maternal toxic doses in rats corresponding to systemic exposure levels similar to the expected clinical exposure.
Eftersom højere eksponeringsniveauer ikke kan testes i dyr på grund af maternel toksicitet, er data for utilstrækkelige til fuldstændig at beskrive lacosamids embryoføtotoksiske og teratogene potentiale.
Since higher exposure levels could not be tested in animals due to maternal toxicity, data are insufficient to fully characterise the embryofetotoxic and teratogenic potential of lacosamide.
Studier med rotter viste, at lacosamid og/ eller dets metabolitter nemt krydsede placentabarrieren.
Studies in rats revealed that lacosamide and/ or its metabolites readily crossed the placental barrier.
Mikrokrystallinsk cellulose Hydroxypropylcellulose Hydroxypropylcellulose (lavsubstitueret) Silica, kolloid vandfri Crospovidon Magnesiumstearat
Tablet core: microcrystalline cellulose hydroxypropylcellulose hydroxypropylcellulose (low substituted) silica, colloidal, anhydrous crospovidone magnesium stearate
Polyvinylalkohol Polyethylenglycol 400, 3350 og 8000 Talkum Soya- lecithin Hypromellose Titandioxid (E171) Rød jernoxid (E172), sort jernoxid (E172), indigocarmin aluminium lake (E132)
Tablet coat: polyvinyl alcohol polyethylene glycol 400, 3350 and 8000 talc soya-lecithin hypromellose titanium dioxide (E171) red iron oxide (E172), black iron oxide (E172), indigo carmine aluminium lake (E132)
8 3 år.
3 years.
PVC/ PVDC / blister med aluminiumsfolie.
PVC/ PVDC blister sealed with an aluminium foil.
Pakninger med 14, 56 og 168 filmovertrukne tabletter
8 Packs of 14, 56 and 168 film-coated tablets.
UCB Pharma SA Allée de la Recherche 60 B- 1070 Bruxelles Belgien
UCB Pharma SA Allée de la Recherche 60 B-1070 Bruxelles Belgium
29. august 2008
29 August 2008
Hver filmovertrukket tablet indeholder 0, 34 mg soyalecithin.
Each film-coated tablet contains 0.34 mg soya-lecithin.
Filmovertrukket tablet Mørkegul, oval filmovertrukket tablet præget med ‘ SP ’ på den ene side og ‘ 100 ’ på den anden.
Film-coated tablet Dark yellow, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 100’ on the other side.
10 Ældre (over 65 år) Dosisjustering er ikke nødvendig hos ældre patienter.
Use in elderly (over 65 years of age) No dose reduction is necessary in elderly patients.
Aldersrelateret nedsat renal clearance med en stigning i AUC- niveauerne bør overvejes hos ældre patienter (se ‘ Patienter med nedsat nyrefunktion ’ ovenfor og pkt.
Age associated decreased renal clearance with an increase in AUC levels should be considered in elderly patients (see ‘ Use in patients with renal impairment’ above and section
5. 2).
10 5.2).
11 Antiepileptika I interaktionsforsøg påvirkede lacosamid ikke signifikant plasmakoncentrationen af carbamazepin og valproinsyre.
Antiepileptic drugs In interaction trials lacosamide did not significantly affect the plasma concentrations of carbamazepine and valproic acid.
Plasmakoncentrationen af lacosamid blev ikke påvirket af carbamazapin eller valproinsyre.
11 valproic acid.
12 fokale anfald, fandt man, at i alt 61, 9% af patienterne, der blev randomiseret til behandling med lacosamid, og 35, 2% af patienterne, der blev randomiseret til behandling med placebo, rapporterede mindst 1 bivirkning.
Based on the analysis of pooled placebo-controlled clinical trials in 1,308 patients with partial-onset seizures, a total of 61.9% of patients randomized to lacosamide and 35.2% of patients randomized to placebo reported at least 1 adverse reaction.
De mest almindeligt rapporterede bivirkninger ved lacosamidbehandling var svimmelhed, hovedpine, kvalme og diplopi (dobbeltsyn).
They were usually mild to
De var som regel milde til moderate.
12 moderate in intensity.
13 taget sammen med toksiske doser af flere andre antiepileptika.
The subject was initially comatose and then fully recovered without permanent sequelae.
Farmakoterapeutisk gruppe: øvrige antiepileptika, ATC- kode:
13 Pharmacotherapeutic group: other antiepileptics, ATC code:
14 Metabolisme 95% af dosis udskilles i urinen som lacosamid og metabolitter.
Metabolism 95% of the dose is excreted in the urine as drug and metabolites.
CYP2C19 er primært ansvarlig for dannelsen af O- desmethyl- metabolitten.
CYP2C19 is mainly responsible for the formation of the O-desmethyl metabolite.
Der blev imidlertid ikke observeret nogen klinisk relevant forskel i eksponeringen for lacosamid, når man sammenlignede med farmakokinetikken hos patienter med hurtig metabolisering (med et funktionelt CYP2C19 enzym) og patienter med langsom metabolisering (uden et funktionelt CYP2C19 enzym).
However, no clinically relevant difference in lacosamide exposure was observed comparing its pharmacokinetics in
Desuden viste et interaktionsforsøg med omeprazol (CYP2C19- hæmmer) ingen klinisk relevante ændringer i plasmakoncentrationerne af lacosamid, hvilket kunne tyde på, at denne eliminationsvej har mindre betydning.
14 extensive metabolisers (EMs, with a functional CYP2C19) and poor metabolisers (PMs, lacking a functional CYP2C19).
Man har ikke fundet andre enzymer involveret i lacosamid- metabolismen.
Furthermore an interaction trial with omeprazole (CYP2C19-inhibitor) demonstrated no clinically relevant changes in lacosamide plasma concentrations indicating that the importance of this pathway is minor.
I toksicitetsstudierne var de opnåede lacosamid plasmakoncentrationer lig med eller kun en anelse højere end dem, man observerede hos patienter, hvorfor marginen for human eksponering er lille eller ikke- eksisterende.
In the toxicity studies, the plasma concentrations of lacosamide obtained were similar or only marginally higher than those observed in patients, which leaves low or non-existing margins to human exposure
Et farmakologisk sikkerhedsstudie med intravenøs indgift af lacosamid i bedøvede hunde viste kortvarige stigninger i PR- interval og QRS- kompleks og fald i blodtrykket, hvilket højst sandsynligt skyldes kardiodepression.
15 A safety pharmacology study with intravenous administration of lacosamide in anesthetized dogs showed transient increases in PR interval and QRS complex duration and decreases in blood pressure most likely due to a cardiodepressant action.
Polyvinylalkohol Polyethylenglycol 400, 3350 og 8000 Talkum Soya- lecithin Hypromellose Titandioxid (E171) Gul jernoxid (E 172)
Tablet coat: polyvinyl alcohol polyethylene glycol 400, 3350 and 8000 talc soya-lecithin hypromellose titanium dioxide (E171) yellow iron oxide (E172)
16 3 år.
3 years.
Pakninger med 14, 56 og 168 filmovertrukne tabletter
Packs of 14, 56 and 168 film-coated tablets.
Ikke alle pakningsstørrelser er nødvendigvis markedsført.
16 Not all pack sizes may be marketed.
Hver filmovertrukket tablet indeholder 0, 50 mg soyalecithin.
Each film-coated tablet contains 0.50 mg soya-lecithin.
Filmovertrukket tablet Laksefarvet, oval filmovertrukket tablet præget med ‘ SP ’ på den ene side og ‘ 150 ’ på den anden.
Film-coated tablet Salmon, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 150’ on the other side.
18 Ældre (over 65 år) Dosisjustering er ikke nødvendig hos ældre patienter.
Use in elderly (over 65 years of age) No dose reduction is necessary in elderly patients.
5. 2).
18 5.2).
19 Antiepileptika I interaktionsforsøg påvirkede lacosamid ikke signifikant plasmakoncentrationen af carbamazepin og valproinsyre.
19 valproic acid.
Baseret på analysen af poolede placebo- kontrollerede kliniske forsøg, omfattende 1. 308 patienter med
Based on the analysis of pooled placebo-controlled clinical trials in 1,308 patients with partial-onset seizures, a total of 61.9% of patients randomized to lacosamide and 35.2% of patients randomized to placebo reported at least 1 adverse reaction.
20 fokale anfald, fandt man, at i alt 61, 9% af patienterne, der blev randomiseret til behandling med lacosamid, og 35, 2% af patienterne, der blev randomiseret til behandling med placebo, rapporterede mindst 1 bivirkning.
20 moderate in intensity.
21 taget sammen med toksiske doser af flere andre antiepileptika.
The subject was initially comatose and then fully recovered without permanent sequelae.
Farmakoterapeutisk gruppe: øvrige antiepileptika, ATC- kode:
21 Pharmacotherapeutic group: other antiepileptics, ATC code:
22 Metabolisme 95% af dosis udskilles i urinen som lacosamid og metabolitter.
Metabolism 95% of the dose is excreted in the urine as drug and metabolites.