qanastek/EMEA-V3 huggingface dataset:
Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicine (see section 4.8).
Għalhekk, il- pazjenti għandhom jingħataw parir biex joqogħdu attenti sakemm isiru familjari mall- effetti potenzjali tal- mediċina (ara sezzjoni 4. 8).
Prolongations in PR interval with lacosamide have been observed in clinical studies.
Ġie osservat titwil fl- interval PR b’ lacosamide f’ studji kliniċi.
Lacosamide should be used with caution in patients with known conduction problems or severe cardiac disease such as a history of myocardial infarction or heart failure.
Lacosamide għandu jintuża b’ kawtela f’ pazjenti bi problemi magħrufa ta ’ konduzzjoni jew mard tal- qalb sever bħal storja ta ’ infart mijokardijaku jew insuffiċjenza tal- qalb.
Caution should especially be exerted when treating elderly patients as they may be at an increased risk of cardiac disorders or when lacosamide is used in combination with products known to be associated with PR prolongation.
Għandha tintuża b’ kawtela f’ pazjenti anzjani trattati għaliex jistgħu jkunu f’ riskju ogħla ta ’ mard tal- qalb jew meta lacosamide jintuża flimkien ma ’ prodotti mediċinali li magħrufa li huma assoċjati ma ’ titwil fil- PR.
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications.
Ħsibijiet u mġieba suwiċidali kienu rrappurtati f’ pazjenti kkurati b ’ mediċini ta ’ kontra l- epilessija f ’ ħafna indikazzjonijiet.
A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour.
Meta- analiżi ta ’ provi bl- addoċċ u kkontrollati mill- plaċebo ta ’ mediċini ta ’ kontra l- epilessija juri żieda żgħira fir- riskju ta ’ ħsibijiet u mġieba suwiċidali.
The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lacosamide.
Il- mekkaniżmu ta ’ dan ir- riskju mhux magħruf u d- dejta preżenti ma teskludix il- possibilta ’ ta ’ żieda fir- riskju b ’ lacosamide.
Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.
Għalhekk il- pazjenti għandhom jiġu ċċekkjati għal sinjali ta ’ ħsibijiet u mġieba suwiċidali u għandu jitqies trattament xieraq.
Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
Il- pazjenti (u dawk li jieħdu ħsieb il- pazjenti) għandhom jingħataw il- parir li jfittxu parir mediku jekk jitfaċċaw sinjali ta ’ ħsibijiet u mġieba suwiċidali.
Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation (e. g. carbamazepine, lamotrigine, pregabalin) and in patients treated with class I antiarrhythmic drugs.
Lacosamide għandu jintuża b’ kawtela f’ pazjenti li huma trattati b ’ prodotti mediċinali magħrufa li huma assoċjati ma ’ titwil fil- PR (eż. carbamazepine, lamotrigine, pregabalin) u f ’ pazjenti trattati b’ mediċini anti- arritmiċi ta ’ klassi I.
However, subgroup analysis did not identify an increased magnitude of PR prolongation in patients with concomitant administration of carbamazepine or lamotrigine in clinical trials.
Iżda, f’ studji kliniċi, analiżi tas- sub- grupp ma identifikax żieda fil - kobor ta ’ titwil fil- PR f’ pazjenti li jkunu qegħdin jieħdu carbamazepine jew lamotrigine fi provi kliniċi.
Data generally suggest that lacosamide has a low interaction potential.
Id- dejta ġeneralment jissuġġerixxi li lacosamide għandu potenzjal baxx għal interazzjoni bejn mediċina u oħra.
In vitro studies indicate that the enzymes CYP1A2, 2B6, and 2C9 are not induced and that CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, and 2E1 are not inhibited by lacosamide at plasma concentrations observed in clinical trials.
Studji in vitro juru li enżimi CPY1A2, 2B9, u 2C9 ma kienux indotti u li CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, u 2E1 ma kienux inhibiti minn lacosamide fil- konċentrazzjonijiet tal - plażma osservati fil- provi kliniċi.
An in vitro study indicated that lacosamide is not transported by P-glycoprotein in the intestine.
Studju in- vitro jindika li lacosamide ma jiġiex trasportat minn P - - glycoprotein fl- imsaren.
Lacosamide does not inhibit or induce the enzyme CYP2C19 in vivo.
Lacosamide ma jinibixxix jew ma jindottax l- enżim CYP2C19 in vivo.
The clinical relevance of this is presently unknown.
Studji in vitro jindikaw li lacosamide jista ’ jkun inhibitur u indottur debboli ta ’ CYP3A4. Ir- rilevanza klinika ta ’ dan bħalissa mhux magħruf.
An interaction study with carbamazepine does not indicate a marked inhibitory effect of lacosamide on CYP3A4 catalysed metabolism at therapeutic doses.
Studju dwar l- effett ta ’ b’ carbamazepine fuq l- effett farmaċewtiku ma jindikax effett inibitorju notevoli ta ’ lacosamide fuq il- metaboliżmu katalizzat b ’ CYP3A4 f’ dożi terapewtiċi.
Strong enzyme inducers such as rifampicin or St John´s wort (Hypericum perforatum) may moderately reduce the systemic exposure of lacosamide.
3 Mediċini li jindottaw l- enzimi b’ mod b’ saħħtu bħal rifampicin u St John’ s Wort (Hypericum perforatum) jistgħu jnaqqsu moderatament l- esponiment sistemiku ta ’ lacosamide.
Therefore, starting or ending treatment with these enzyme inducers should be done with caution.
Għalhekk, il- bidu jew it- tmiem tal- kura b’ dawn il- mediċini li jindottaw l- enżimi għandu jsir b’ kawtela.
Antiepileptic drugs In interaction trials lacosamide did not significantly affect the plasma concentrations of carbamazepine
Mediċini ta ’ kontra l- epilessija Fi provi dwar l- effett ta ’ mediċini fuq l- effett farmaċewtiku tal- prodott, lacosamide ma kellux effett sinifikanti fuq il- konċentrazzjoni fil- plażma ta ’ carbamazepine u valproic acid.
Lacosamide plasma concentrations were not affected by carbamazepine and by valproic acid.
Il- konċentrazzjoni fil - plażma ta ’ lacosamide ma kienx affetwat b’ carbamazepine u valproic acid.
A population PK analysis estimated that concomitant treatment with other anti-epileptic drugs known to be enzyme inducers (carbamazepine, phenytoin, phenobarbital, in various doses) decreased the overall systemic exposure of lacosamide by 25%.
Analiżi tal- PK fil - populazzjoni ħarġet stima li trattament flimkien ma ’ mediċini oħra magħrufa li jindottaw l- enżimi (carbamazepine, phenytoin, phenobarbital, f’ dożi varji) naqset l- esponiment sistemiku totali ta ’ lacosamide b’ 25%..
Oral contraceptives In an interaction trial there was no clinically relevant interaction between lacosamide and the oral contraceptives ethinylestradiol and levonorgestrel.
Kontraċettivi orali Provi dwar l- effett ta ’ mediċini fuq l- effett farmaċewtiku tal- prodott wrew li ma kien hemm ebda effett klinikament rilevanti bejn lacosamide u l- kontraċettivi orali ethinylestradiol u levonorgestrel.
Progesterone concentrations were not affected when the medicinal products were co-administered.
Il - konċentrazzjonijiet ta ’ progesterone ma kienux affetwati meta l- prodotti mediċinali ngħataw flimkien.
Others Interaction trials showed that lacosamide had no effect on the pharmacokinetics of digoxin.
Oħrajn Provi dwar l- effett ta ’ mediċini fuq l- effett farmaċewtiku tal- prodott wrew li lacosamide ma kellux effett fuq il- farmakokinetika ta ’ digoxin.
There was no clinically relevant interaction between lacosamide and metformin.
Ma kienx hemm effett klinikament relevanti bejn lacosamide u metformin.
Omeprazole 40 mg q. d. increased the AUC of lacosamide by 19%.
Omeprazole 40 mg q. d. żied l- AUC ta ’ lacosamide b ’ 19%.
The effect probably lacks clinical relevance.
L- effett probabilment m’ għandux rilevanza klinika.
Lacosamide did not affect the single-dose pharmacokinetics of omeprazole.
Lacosamide ma kellux effett fuq il- farmakokinetika ta ’ doża waħda ta ’ omeprazole.
No data on the interaction of lacosamide with alcohol are available.
M’ hemmx tagħrif fuq l- effett ta ’ lacosamide ma ’ l- alkoħol.
Lacosamide has a low protein binding of less than 15%.
Lacosamide jeħel mal- protejini tad- demm b’ rata baxxa ta ’ 15%.
Therefore, clinically relevant interactions with other drugs through competition for protein binding sites are considered unlikely.
Għalhekk mhux probabli li jkun hemm effetti klinikament relevanti ma ’ mediċini oħra permezz ta ’ kompetizzjoni għal postijiet fejn jeħlu l- protejini.
Pregnancy Risk related to epilepsy and antiepileptic medicinal products in general For all anti-epileptic drugs, it has been shown that in the offspring of women treated with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population.
Tqala Ir- riskju ġeneralment relatat ma ’ l- epilessija u ma ’ prodotti mediċinali ta ’ kontra l- epilessija kien muri li, għal mediċini ta ’ kontra l- epilessija kollha, l- inċidenza ta’ malformazzjonijiet fl- ulied ta ’ nisa trattati għal epilessija, hija darbtejn għal tlett darbiet aktar mir- rata ta ’ madwar 3% fil - popolazzjoni ġenerali.
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.
Fil- popolazzjoni fuq trattament, kienet innotata żieda fil- malformazzjonijiet b’ politerapija, iżda, għadu mhux ċar kemm dan huwa dovut għat- trattament u/ jew il- marda.
Moreover, effective anti-epileptic therapy must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.
Madanakollu, m’ għandiex titwaqqaf terapija effettiva ta ’ kontra l- epilessija, għaliex meta tiggrava l - marda tkun ta ’ detriment għall- omm u l- fetu.
Risk related to lacosamide There are no adequate data from the use of lacosamide in pregnant women.
Riskju relatat ma ’ lacosamide M’ hemmx tagħrif adekwat fuq l- użu ta ’ lacosamide f’ nisa tqal.
Studies in animals did not indicate any teratogenic effects in rats or rabbits, but embyrotoxicity was observed in rats and rabbits at maternal toxic doses (see section 5.3).
Studji fl- annimali ma ’ wrewx effetti teratoġeniċi fuq il- fetu, fil- firien jew fniek, iżda f’ dożi tossiċi għall- omm, ġiet osservata tossiċita` fuq l- embriju, fil- firien u fil- fniek (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Mhux magħruf ir- riskju potenzjali għal bniedem.
Lacosamide should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus).
Lacosamide m’ għandux jintuża waqt it- tqala sakemm mhux ovvjament neċessarju (jekk il- benefiċċju għall- omm jiżboqq ir- riskju potenzjali għal fetu).
If women decide to become pregnant, the use of this product should be carefully re-evaluated.
L’ użu ta ’ dan il- prodott irid jerġa’ jiġi meqjus sew meta nisa jiddeċiedu li joħorġu tqal.
Lactation It is unknown whether lacosamide is excreted in human breast milk.
Treddiegħ Mhux magħruf jekk lacosamide jinħeriex fil- ħalib ta’ l- omm fil- bniedem.
Animal studies have shown excretion of lacosamide in breast milk.
Studji fl- annimali juri l - eskrezzjoni ta ’ lacosamide fil- ħalib tas- sider.
For precautionary measures, breast-feeding should be discontinued during treatment with lacosamide.
Bħala miżuri ta ’ prekawzjoni, it- treddiegħ għandu jitwaqqaf waqt trattament b ’ lacosamide.
Vimpat may have minor to moderate influence on the ability to drive and use machines.
4 Vimpat jista ’ jkollu effett minn żgħir għal moderat fuq il- ħila biex issuq u tħaddem magni.
Vimpat treatment has been associated with dizziness or blurred vision.
Il- kura b’ Vimpat kienet assoċjata ma ’ sturdament jew vista mċajpra.
Accordingly, patients should be advised not to drive a car or to operate other potentially hazardous machinery until they are familiar with the effects of Vimpat on their ability to perform such activities.
Għalhekk, il- pazjenti għandhom jingħataw parir biex ma jsuqux jew iħaddmu magni li jistgħu jkunu perikolużi qabel ma jidraw l- effetti ta ’ Vimpat fuq il- ħila tagħhom f’ dawn l- attivitajjiet.
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.
Skond l- analiżi ta ’ provi kliniċi ikkontrollati bil- plaċebo miġbura minn 1, 308 pazjent b ’ aċċessjonijiet tat- tip partial- onset, total ta ’ 61. 9% tal- pazjenti magħżula bl- addoċċ biex jieħdu lacosamide u 35. 2% tal- pazjenti magħżula bl- addoċċ biex jieħdu l- plaċebo irrappurtaw mill- inqas reazzjoni mhux mixtieq wieħed.
The most frequently reported adverse reactions with
L- iżjed effett mhux mixtieq li ġie rappurtat b’ lacosamide kienu sturdament, uġigħ ta ’ ras, dardir u diplowpja.
They were usually mild to moderate in intensity.
Dawn ħafna drabi kienu effetti ħfief għal moderati.
Some were dose-related and could be alleviated by reducing the dose.
Ftit kienu relatati ma- doża u setgħu jittaffew bi tnnaqqis fid- doża.
Incidence and severity of CNS and gastrointestinal (GI) adverse reactions usually decreased over time.
L- inċidenza u s- severita` ta ’ effetti mhux mixtieqa tas - CNS u gastro- intestinali (GI) issoltu naqsu biż- żmien.
Over all controlled studies, the discontinuation rate due to adverse reactions was 12.2% for patients randomized to lacosamide and 1.6% for patients randomized to placebo.
Fl- istudji kollha, ir- rata ta ’ twaqqif minħabba l- effetti mhux mixtieqa kienet ta ’ 12. 2% għal pazjenti li kienu randomised fuq lacosamide u 1. 6% għal pazjenti randomised fuq il- plaċebo.
The most common adverse reaction resulting in discontinuation of lacosamide therapy was dizziness.
L- iżjed effett mhux mixtieq li wassal għat- twaqqif ta ’ lacosamide kien sturdament.
The table below shows the frequencies of adverse reactions which have been reported in pooled placebo-controlled clinical trials.
It- tabella hawn taħt turi l- frekwenza ta ’ l- effetti mhux mixtieqa li ġew rapportati f’ ġabra ta’ provi kliniċi ikkontrolati mill- plaċebo.
The frequencies are defined as follows: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100).
Il- frekwenzi ġew definiti bħala: komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10), mhux komuni (≥1/ 1, 000 sa < 1/ 100).
System organ class
Sistema ta ’ klassifika tal- organi
Balance disorder Coordination abnormal Memory impairment Cognitive disorder Somnolence Tremor Nystagmus
Taqlib tal- bilanċ Ko- ordinazzjoni abnormali Indeboliment tal - memorja Mard tal - konjizzjoni Ngħas Rogħda Nystagmus
Eye disorders Ear and labyrinth disorders
Mard ta ’ l- għajnejn Mard tal- widnejn u tas- sistema labirintika
Diplopia
Diplowpja
Vision blurred Vertigo
Viżżjoni mċajpra Vertigo
Gastrointestinal disorders
Mard gastro - intestinali
Vomiting Constipation Flatulence
Rimettar Stitikezza Uġigħ ta ’ gas fl - istonku
Skin and subcutaneous tissue disorders
Mard tal- ġilda u tat - tessut ta ’ taħt il- ġilda
General disorders and administration site conditions Injury, poisoning and procedural complications
Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata Korriment, avvelenament u komplikazzonijiet ta ’ xi proċedura
Gait disturbance Asthenia Fatigue Fall Skin laceration
Diffikulta` fil- mixi Astenja Għajja Waqgħa Feriti fil- ġilda
The use of lacosamide is associated with dose-related increase in the PR interval.
5 L’ użu ta ’ lacosamide huwa assoċjat b’ żieda marbuta mad- doża fl- interval PR.
Adverse reactions associated with PR interval prolongation (e. g. atrioventricular block, syncope, bradycardia) may occur.
Ir- reazzjonijiet mhux mixtieqa assoċjati ma ’ titwil tal- interval PR (eż. blokk atrijoventrikulari, sinkope, bradikardja) jistgħu jseħħu.
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.
F’ pazjenti epilettiċi, r- rata ta’ l- inċidenza ta ’ blokk AV ta ’ l- ewwel grad rappurtat mhuwiex komuni, 0. 7%, 0%, 0. 5% u 0% għal lacosamide 200 mg, 400 mg, 600 mg jew placebo, rispettivament.
No second or higher degree AV Block was seen in lacosamide treated patients.
Ma dehrux blokk AV tat- tieni jew ogħla grad f’ pazjenti trattati b’ lacosamide.
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%).
Ir- rata ta ’ l- inċidenza ta ’ sinkope mhux komuni u ma kienitx differenti bejn pazjenti trattati b’ lacosamide (0. 1%) u dawk trattati bil- plaċebo (0. 3%).
There is limited clinical experience with lacosamide overdose in humans.
Hemm esperjenza klinika limitata b’ doża eċċessiva ta ’ lacosamide.
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.
Sintomi kliniċi (sturdament u dardir) wara dożi ta ’ 1200 mg/ ġurnata kienu ġeneralment relatati mas- sistema ċentrali nervuża u s - sistema gastro- intestinali, u għaddew wara aġġustamenti fid- doża.
The subject was initially comatose and then fully recovered without permanent sequelae.
L’ ogħla doża eċċessiva li ġiet rapportata fil- programm taż- żvillup ta ’ lacosamide kien b ’ 12 g li ttieħed flimkien ma ’ dożi tossiċi ta ’ diversi mediċini ta ’ kontra l- epilessija oħra. Għall- ewwel il - persuna kienet f’ koma u mbagħad għaddielha kompletament mingħajr konsegwenzi permanenti.
There is no specific antidote for overdose with lacosamide.
M’ hemmx antidotu specifiku għal doża eċċessiva b’ lacosamide.
Treatment of lacosamide overdose should include general supportive measures and may include haemodialysis if necessary (see section 5.2).
It- trattament ta ’ doża eċċessiva b’ lacosamide għandha tinkludi miżuri ġenerali ta ’ appoġġ u jekk ikun necessarju tista ’ tinkludi emodijaliżi (ara sezzjoni 5. 2)
Pharmacotherapeutic group: other antiepileptics, ATC code:
Kategorija farmakoterapewtika: mediċini ta ’ kontra l- epilessija oħra, Kodiċi ATC:
N03AX18 The active substance, lacosamide (R-2-acetamido-N-benzyl-3-methoxypropionamide) is a functionalised amino acid.
N03AX18 Is- sustanza attiva, lacosamide (R- 2- acetamido- N- benzyl- 3- methoxypropionamide) huwa amino- aċidu funzjonalizzat.
Mechanism of action The precise mechanism by which lacosamide exerts its antiepileptic effect in humans remains to be fully elucidated.
Mekkaniżmu t ’ azzjoni Il- mekkaniżmu preċis li bih lacosamide jagħmel l- effett tiegħu ta ’ kontra l- epilessija għadu mhux ċar għal kollox.
Two observations that may be of relevance for the observed therapeutic effects are:
Żewġt osservazzjonijet li jistgħu jkunu relevanti għall- effetti terapewtiċi li ġew osservati huma:
In vitro electrophysiological studies have shown that lacosamide selectively enhances slow inactivation of voltage-gated sodium channels, resulting in stabilization of hyperexcitable neuronal membranes.
Studji in vitro elettrofiżjoloġiċi wrew li lacosamide jinkoraġġixxi selettivament l- inattivazzjoni bil - mod tal- kanali voltage- gated tas- sodium, li jirrisulta fl- istabilta` tal- membrani newronali ipereċċitabbli.
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.
Barra minn hekk, lacosamide jeħel mal- collapsin response mediator protein- 2 (CRMP- 2), fosfoproteina li issibu prinċipalment fis- sistema nervuża u huwa involut fid - differenzazzjoni newronali u l- kontrol ta’ l- żvillup axonali.
Pharmacodynamic effects Lacosamide protected against seizures in a broad range of animal models of partial and primary generalized seizures and delayed kindling development.
Effetti farmakodinamiċi Lacosamide kellu protezzjoni kontra l- aċċessjonijiet f’ medda wiesgħa ta ’ mudella fl- annimali ta ’ aċċessjonijiet tat- tip parzjali u primarji ġeneralizzati u ttardja l- iżvillup tal- kindling.
In non-clinical experiments lacosamide in combination with levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, topiramate or gabapentin showed synergistic or additive anticonvulsant effects.
F’ esperimenti mhux kliniċi, lacosamide flimkien ma ’ levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, topiramide jew gabapentin wera effetti ta ’ kontra l- epilessija sinerġistiċi jew addittivi.
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.
Esperjenza klinika L- effikaċja ta ’ Vimpat bħala terapija aġġuntiva fid- dożi rrikkmandati (200 mg/ ġurnata, 400 mg/ ġurnata) kienet stabbilita fi tlett provi kliniċi, kontrollati mill- plaċebo, randomized u multiċentrali, b ’ perjodu ta ’ manteniment ta 12- il ġimgħa.
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.
Vimpat 600 mg/ ġurnata kien muri effettiv fi provi b’ terapija miżjuda kkontrollati, għalkemm l- effikaċja kienet simili għal 400 mg/ ġurnata u l - pazjenti x’ aktarx inqas ittolleraw din id- doża minħabba reazzjonijiet mhux mixtieqa relatati mas- CNS u dawk gastro- intestinali.
Thus, the 600 mg/ day dose is not recommended.
Għalhekk, id- doża ta ’ 600 mg/ ġurnata mhix irrikkmandata.
The maximum recommended dose is 400 mg/ day.
Id- doża massima rrikkmandata hija 400 mg/ ġurnata.
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.
Dawn il- provi li inkludew 1308 pazjenti b’ storja ta ’ medja ta ’ 23 sena ta ’ aċċessjonijiet ta ’ tip partial onset, kienu ddiżinjati sabiex jitkejlu l- effikaċja u s- sigurta ’ ta ’ lacosamide meta jingħata flimkien ma ’ 1- 3 mediċini ta ’ kontra l- epilessija f’ pazjenti b ’ aċċessjonijiet
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.
Il - proporzjon ta ’ persuni fuq kollox bi tnaqqis ta ’ 50% fil- frekwenza ta ’ aċċessjonijiet kien ta ’ 23%, 34%, u 40% għal- plaċebo, lacosamide 200 mg/ ġurnata u lacosamide 400 mg/ ġurnata.
There are insufficient data regarding the withdrawal of concomitant antiepileptic medicinal products to achieve monotherapy with lacosamide.
M’ hemmx dejta biżżejjed rigward it- twaqqif ta ’ mediċina ta ’ kontra l- epilessija li jingħataw flimkien biex tibda monoterapija b ’ lacosamide.
Absorption Lacosamide is rapidly and completely absorbed after oral administration.
Assorbiment Lacosamide huwa assorbit rapidament u kompletament wara amministrazzjoni mill- ħalq.
The oral bioavailability of lacosamide tablets is approximately 100%.
Il - biodisponibilta` orali ta ’ lacosamide hija madwar 100%.
Following oral administration, the plasma concentration of unchanged lacosamide increases rapidly and reaches Cmax about 0.5 to 4 hours post-dose.
Wara amministrazzjoni mill- ħalq, il - konċentrazzjonijiet tal- plażma ta ’ lacosamide mhux mibdul tiżdied malajr u tilħaq Cmax madwar 0. 5 sa 4 sigħat wara d- doża.
Vimpat tablets and oral syrup are bioequivalent.
Vimpat pilloli u mistura orali huma bio- ekwivalenti.
Food does not affect the rate and extent of absorption.
L- ikel ma jaffettwax ir - rata u l- livell ta ’ assorbiment.
Distribution The volume of distribution is approximately 0.6 L/ kg.
Distribuzzjoni Il- volum ta ’ distribuzzjoni huwa madwar 0. 6 L/ kg.
Lacosamide is less than 15% bound to plasma proteins.
Lacosamide huwa marbut b ’ inqas minn 15% mal - proteini fil- plażma.
Metabolism 95% of the dose is excreted in the urine as drug and metabolites.
Metaboliżmu 95% tad- doża hija mneħħija fl- awrina bħala mediċina u prodott tal- metaboliżmu.
The metabolism of lacosamide has not been completely characterised.
Il- metaboliżmu ta ’ lacosamide ma kienx kompletament ikkaratterizzat.
The major compounds excreted in urine are unchanged lacosamide (approximately 40% of the dose) and its O-desmethyl metabolite less than 30%.
Is- sustanzi prinċipali li kienu eskretti fl- awrina me kienux mibdulin lacosamide (madwar 40% tad- doża) u l- prodott tal- metaboliżmu tiegħu O- desmethyl (inqas minn 30%).
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.
Frazzjoni polari li kienet proposta li tikkonsisti f ’ derivattivi ta ’ serine għamlet madwar 20% fl- awrina, imma kienet misjuba biss f’ ammonti żgħar (0- 2%) fil- plażma umana ta ’ xi pazjenti.
Small amounts (0.5-2%) of additional metabolites were found in the urine.
Ammonti żgħar (0. 5- 2%) ta ’ prodotti tal- metaboliżmu addizjonali kienu misjuba fl- awrina.
However, no
CYP2C19 huwa riponsabli prinċipalment għall- formazzjoni tal- prodott tal- metaboliżmu O - desmethyl.
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).
Madanakollu, ma kinitx osservata differenza klinikament relevanti fl- esponiment ta ’ lacosamide meta tqabbel il- farmakokinetika tiegħu f’ metabolizzanti estensivi (EMs, b ’ CYP2C19 funzjonali) u l- metabolizzanti deboli (PMs, li m’ għandhomx CYP2C19 funzjonali).
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.
Barra minn dan, prova ta 'interazzjoni b ’ omeprazole (inibitur- CYP 2C19) m’ urietx tibdil klinikament relevanti fil - konċentrazzjonijiet ta ’ lacosamide fil- plażma li indika li l- importanza ta ’ dan is- sensiela ta ’ reazzjonijiet hija żgħira.
No other enzymes have been identified to be involved in the metabolism of lacosamide.
Ebda enżim ieħor ma kien identifikat li hu involut fil- metaboliżmu ta ’ lacosamide.
The plasma concentration of O-desmethyl-lacosamide is approximately 15% of the concentration of lacosamide in plasma.
Il- konċentrazzjoni tal- plażma ta ’ O- desmethyl- lacosamide huwa madwar 15% tal- konċentrazzjoni ta ’ lacosamide fil- plażma.
This major metabolite has no known pharmacological activity.
Dan il- prodott prinċipali tal- metaboliżmu m’ għandux attivita` farmakoloġika magħrufa.
Elimination Lacosamide is primarily eliminated from the systemic circulation by renal excretion and biotransformation.
Eliminazzjoni Lacosamide huwa eliminat primarjament miċ- ċirkulazzjoni sistemika b’ eskrezzjoni renali u bijotrasformazzjoni.
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.
Wara t- teħid orali u minn ġol- vina ta ’ lacosamide radjutikkettat, madwar 95% tar - radju- attivita` li ngħatat kienet misjuba fl- awrina u inqas minn 0. 5% fl- ippurgar.
The elimination half-life of the unchanged drug is approximately 13 hours.
Il- half- life ta ’ eliminazzjoni tal- mediċina mhux mibdula kienet ta ’ madwar 13- il siegħa.
The pharmacokinetics is dose-proportional and constant over time, with low intra- and inter-subject variability.
Il - farmakokinetika hija proporzjonali mad- doża u kostanti maż- żmien, b ’ varjabilita` baxxa kemm fl- istess persuni kif ukoll bejn il- persuni differenti.
Following twice daily dosing, steady state plasma concentrations are achieved after a 3 day period.
Wara dożaġġ ta ’ darbtejn kuljum, intlaħqu konċentrazzjoni fil- plażma fi stat fiss, wara perjodu ta ’ tlett ijiem.
The plasma concentration increases with an accumulation factor of approximately 2.
Il- konċentrazzjoni fil- plażma żdiedu b’ fattur ta ’ akkumulazzjoni ta ’ madwar 2.
Pharmacokinetics in special patient groups Gender Clinical trials indicate that gender does not have a clinically significant influence on the plasma concentrations of lacosamide.
Farmakokinetika f’ gruppi speċjali ta ’ pazjenti Sess Provi kliniċi juru li s- sess m’ għandux influenza klinikament sinifikanti fuq konċentrazzjoni fil- plażma ta ’ lacosamide.
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.
7 L’ AUC ta ’ lacosamide żdiedet b’ madwar 30% f’ pazjenti b’ indeboliment renali baxx u moderat u 60% f’ pazjenti b’ indeboliment renali sever u f’ pazjenti b’ mard renali fl- istadji ta ’ l- aħħar fejn hemm bżonn ta ’ emodijaliżi, meta mqabbel ma ’ pazjenti f’ saħħithom, iżda cmax ma ġiex affettwat.
Lacosamide is effectively removed from plasma by haemodialysis.
Lacosamide huwa effettivament imneħħi mill- plażma b’ emodijaliżi.
Following a 4-hour haemodialysis treatment, AUC of lacosamide is reduced by approximately 50%.
Wara trattament t’ emodijaliżi ta ’ 4 sigħat, AUC ta ’ lacosamide kien mnaqqas b ’ madwar 50%.
Therefore dosage supplementation following haemodialysis is recommended (see section 4.2).
Għalhekk huwa rrikkmandat suppliment fid- dożaġġ wara l- emodijaliżi (ara sezzjoni 4. 2). L- esponiment tal – prodott tal- metaboliżmu O- desmethyl kien miżjud b’ diversi drabi f’ pazjenti b’ indeboliment moderat jew sever.
The exposure of the O-desmethyl metabolite was several-fold increased in patients with moderate and severe renal impairment.
Meta ma kienx hemm emodijaliżi f’ pazjenti b’ mard tal- kliewi fl- aħħar fażi, il- livelli kienu ogħla u żiedu kontinwament waqt li ttieħdu kampjuni f’ 24 siegħa.
It is unknown whether the increased metabolite exposure in endstage renal disease subjects could give rise to adverse effects but no pharmacological activity of the metabolite has been identified.
Mhux magħruf jekk iż- żieda fl- esponiment tal - prodott tal- metaboliżmu f’ pazjenti b’ mard tal- kliewi fl- aħħar fażi, jistax jikkawża effetti mhux mixtieqa iżda ma ġiex identifikat ebda attivita` farmakoloġika tal- prodott tal- metaboliżmu.
Hepatic impairment Subjects with moderate hepatic impairment (Child-Pugh B) showed higher plasma concentrations of lacosamide (approximately 50% higher AUCnorm).
Indeboliment tal- fwied Persuni b’ indeboliment moderat tal- fwied (Child- Pugh B) wrew konċentrazzjoni ogħla ta ’ lacosamide fil- plażma (AUCnorm madwar 50% ogħla).
The higher exposure was partly due to a reduced renal function in the studied subjects.
L- esponiment ogħla kienet dovuta parzjalment għall - funzjoni renali mnaqqsa fil- persuni studjati.
The decrease in non-renal clearance in the patients of the study was estimated to give a 20% increase in the AUC of lacosamide.
It- tnaqqis fil- clearance li ma jsirx fil- kliewi fil- pazjenti fl- istudju, kien stmat li jagħti 20% żieda fl ’ AUC ta ’ lacosamide.
The pharmacokinetics of lacosamide has not been evaluated in severe hepatic impairment (see section 4.2).
Il- farmakokinetika ta ’ lacosamide ma ġiex studjat f ’ indeboliment sever tal- fwied (ara sezzjoni 4. 2).
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.
Anzjani (aktar minn 65 sena) F’ studji fl- anzjani, irġiel u nisa inkluż 4 pazjenti > 75 sena, AUC kien rispettivament madwar 30 u 50% ogħla meta mqabbla ma ’ dak f’ irġiel ta ’ età żgħira.
The body weight normalized difference is 26 and 23%, respectively.
Dan huwa marbut f’ parti ma ’ piż aktar baxx tal- ġisem. Id- differenza normalizzata tal- piz tal- ġisem kienet ta ’ 26 u 23% rispettivament.
An increased variability in exposure was also observed.
Kienet osservata wkoll żieda fil- varjabbilita` ta ’ esponiment.
The renal clearance of lacosamide was only slightly reduced in elderly subjects in this study.
F’ dan l- istudju, it- tneħħija mill- kliewi ta ’ lacosamide kienet mnaqqsa ftit żgħira biss f’ persuni anzjani.
A general dose reduction is not considered to be necessary unless indicated due to reduced renal function (see section 4.2).
Tnaqqis fid- doża ġenerali mhux meqjus neċessarju, sakemm ma jkunx hemm il- bżonn minħabba tnaqqis fil- funzjoni renali (ara sezzjoni 4. 2).
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
F’ studji dwar it- tossiċita`, il- konċentrazzjoni fil- plażma ta ’ lacosamide li kien hemm kienu simili jew ħarira biss ogħla minn dawk osservati f’ pazjenti trattati b’ lacosamide, li tħalli marġini baxxi għal esponimemt fil- bniedem.
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.
Studju farmakoloġika ta ’ sigurta ’ b ’ teħid ġol- vina ta ’ lacosamide f’ klieb anastetiżżati wrew żiediet li jgħaddu fl- interval PR u d- dewmien tal- kumpless QRS u tnaqqis fil- pressjoni tad- demm li huma x’ aktarx minħabba azzjoni kardjodepressanti.
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.
Dawn it- tibdiliet li jgħaddu bdew fl- istess medda ta ’ konċentrazzjoni wara d- dożaġġ massimu kliniku rrikkmandat. F’ dożi li jingħataw ġol- vina ta ’ 15 - 60 mg/ kg f’ klieb anastetiżżati, u f’ xadini Cynomolgus, kienu osservati kondittivita`atrijali u ventrikulari iżjed bil- mod, blokk atrijoventrikulari u dissoċjazzjoni.
In the repeated dose toxicity studies, mild reversible liver changes were observed in rats starting at about 3 times the clinical exposure.
F’ studji dwar l- effett tossiku ta ’ dożi ripetuti, tibdiliet ħfief u riversibli fil- fwied kienu osservati fil - firien minn madwar 3. 6 l- darba l- esponiment kliniku.
These changes included an increased organ weight, hypertrophy of hepatocytes, increases in serum concentrations of liver enzymes and increases in total cholesterol and triglycerides.
Dawn it- tibdiliet jinkludu żieda fil- piz tal - organi, ipertrofija tal- epatoċiti, żieda fil- konċentrazzjoni fis- serum ta ’ enżimi tal- fwied u żieda fit- total tal- kolesterol u trigliċidi.
Apart from the hypertrophy of hepatocytes, no other histopathologic changes were observed.
Minn barra l- ipertrofija tal- epatoċiti, ma deherux tibdiliet istopatoloġiċi oħra.
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.
F’ studji dwar l- effett tossiku fuq ir- riproduzzjoni u l- iżvillup f ’ annimali gerriema u ġrieden, ma kienux osservati effetti teratoġeniċi imma kien hemm żieda fin- numru ta ’ frieħ li twieldu mejta u mwiet ta ’ frieħ fil- perjodu ta ’ wara t- twelid u tnaqqis żgħir ħafna fid- daqs tal- boton u fil- piz tal- frieħ b’ dożi tossiċi fl- omm fil- firien li jikkorrespondu għal livelli ta ’ esponiment sistemiċi simili għal esponiment kliniku mistenni.
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.
Peress li livelli t’ esponiment ogħla ma setgħux jiġu studjati fl - annimali, minħabba tossiċita` fl- omm`, it- tagħrif mhux biżżejjed sabiex juri l- potenzjal għal tossiċita` tal- embriju u l- fetu u teratoġeniċita ta ’ lacosamide.
Studies in rats revealed that lacosamide and/ or its metabolites readily crossed the placental barrier.
Studji fil- firien juri li lacosamide u/ jew il- prodotti tal- metaboliżmu tiegħu jgħaddu faċilment minn ġol - plaċenta.
6.1 List of excipients
8 6. 1 Lista ta ’ sustanzi mhux attivi
Tablet core: microcrystalline cellulose hydroxypropylcellulose hydroxypropylcellulose (low substituted) silica, colloidal, anhydrous crospovidone magnesium stearate
Il- qalba tal- pillola: microcrystalline cellulose hydroxypropylcellulose hydroxypropylcellulose (low substituted) silica, colloidal, anhydrous crospovidone magnesium stearate
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)
Il- kisja tal- pillola: polyvinyl alcohol polyethylene glycol 400, 3350 u 8000 talc soya- lecithin hypromellose titanium dioxide (E171) red iron oxide (E172), black iron oxide (E172), indigo carmine aluminium lake (E132)
This medicinal product does not require any special storage conditions.
Dan il- prodott mediċinal m’ għandux bżonn kundizzjonijiet speċjali ta ’ ħażna.
PVC/ PVDC blister sealed with an aluminium foil.
Folja tal- PVC/ PVDC siġillata b’ fojl ta ’ l- aluminju.
8 Packs of 14, 56 and 168 film-coated tablets.
Pakketti ta ’ 14, 56 u 168 pilloli miksija b’ rita
UCB Pharma SA Allée de la Recherche 60 B-1070 Bruxelles Belgium
UCB Pharma SA Allée de la Recherche 60 B- 1070 Brussel Belġjum
29 August 2008
29 ta ’ Awwissu 2008
Vimpat 100 mg film-coated tablets
Vimpat 100 mg pilloli miksija b’ rita
Each film-coated tablet contains 100 mg lacosamide.
Kull pillola miksija b’ rita fiha 100 mg lacosamide.
Each film-coated tablet contains 0.34 mg soya-lecithin.
Kull pillola miksija b’ rita fiha 0. 34 mg soya- lecithin.
Film-coated tablet Dark yellow, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 100’ on the other side.
Pillola miksija b’ rita ovali, safra skura, b ’ ‘ SP ’ imnaqqxa fuq naħa waħda u ‘ 100 ’ fuq in- naħa l- oħra.
Use in elderly (over 65 years of age) No dose reduction is necessary in elderly patients.
11 Użu fl- anzjani (‘ l fuq minn 65 sena) M’ hemmx bżonn tnaqqis fid- doża f’ pazjenti anzjani.
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
F’ pazjenti anzjani, għandu jitqies it- tnaqqis fil- clearance tal- kliewi b’ żieda fil- livelli AUC assocjat ma ’ l- eta` (ara ‘ Użu f’ pazjenti b’ indeboliment renali ’ hawn fuq u sezzjoni 5. 2).
Strong enzyme inducers such as rifampicin or St John´s wort (Hypericum perforatum) may moderately reduce the systemic exposure of lacosamide.
12 Mediċini li jindottaw l- enzimi b’ mod b’ saħħtu bħal rifampicin u St John’ s Wort (Hypericum perforatum) jistgħu jnaqqsu moderatament l- esponiment sistemiku ta ’ lacosamide.
Antiepileptic drugs In interaction trials lacosamide did not significantly affect the plasma concentrations of carbamazepine and valproic acid.
Mediċini ta ’ kontra l- epilessija Fi provi dwar l- effett ta ’ mediċini fuq l- effett farmaċewtiku tal- prodott, lacosamide ma kellux effett sinifikanti fuq il- konċentrazzjoni fil- plażma ta ’ carbamazepine u valproic acid.
Lacosamide plasma concentrations were not affected by carbamazepine and by
Il- konċentrazzjoni fil - plażma ta ’ lacosamide ma kienx affetwat b’ carbamazepine u valproic acid.
Vimpat may have minor to moderate influence on the ability to drive and use machines.
13 Vimpat jista ’ jkollu effett minn żgħir għal moderat fuq il- ħila biex issuq u tħaddem magni.
They were usually mild to
L- iżjed effett mhux mixtieq li ġie rappurtat b’ lacosamide kienu sturdament, uġigħ ta ’ ras, dardir u diplowpja.
12 moderate in intensity.
Dawn ħafna drabi kienu effetti ħfief għal moderati.
Nervous system disorders
Mard tas- sistema nervuża Mard ta ’ l- għajnejn Diplowpja Viżżjoni mċajpra
Eye disorders Ear and labyrinth disorders
Mard tal- widnejn u tas- sistema labirintika
Vision blurred Vertigo
Vertigo Mard gastro - intestinali Dardir
Gastrointestinal disorders
Rimettar Stitikezza Uġigħ ta ’ gas fl- istonku Mard tal- ġilda u tat- tessut ta ’ taħt il- ġilda
Skin and subcutaneous tissue disorders
Ħakk Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Pruritus
Diffikulta` fil- mixi Astenja
General disorders and administration site conditions Injury, poisoning and procedural complications
14 Għajja Korriment, avvelenament u komplikazzonijiet ta ’ xi proċedura
Gait disturbance Asthenia Fatigue Fall Skin laceration
Waqgħa Feriti fil- ġilda
The use of lacosamide is associated with dose-related increase in the PR interval.
L’ użu ta ’ lacosamide huwa assoċjat b’ żieda marbuta mad- doża fl- interval PR.
13 Pharmacotherapeutic group: other antiepileptics, ATC code:
Kategorija farmakoterapewtika: mediċini ta ’ kontra l- epilessija oħra, Kodiċi ATC:
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.
Vimpat 600 mg/ ġurnata kien muri effettiv fi 15 provi b’ terapija miżjuda kkontrollati, għalkemm l- effikaċja kienet simili għal 400 mg/ ġurnata u l - pazjenti x’ aktarx inqas ittolleraw din id- doża minħabba reazzjonijiet mhux mixtieqa relatati mas- CNS u dawk gastro- intestinali.
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.
Dawn il- provi li inkludew 1308 pazjenti b’ storja ta ’ medja ta ’ 23 sena ta ’ aċċessjonijiet ta ’ tip partial onset, kienu ddiżinjati sabiex jitkejlu l- effikaċja u s- sigurta ’ ta ’ lacosamide meta jingħata flimkien ma ’ 1- 3 mediċini ta ’ kontra l- epilessija f’ pazjenti b ’ aċċessjonijiet mhux kontrollati tat- tip partial onset kemm bi kif ukoll mingħajr ġeneralizzazzjoni sekondarja.
CYP2C19 is mainly responsible for the formation of the O-desmethyl metabolite.
CYP2C19 huwa riponsabli prinċipalment għall- formazzjoni tal- prodott tal- metaboliżmu O - desmethyl.
14 extensive metabolisers (EMs, with a functional CYP2C19) and poor metabolisers (PMs, lacking a functional CYP2C19).
Madanakollu, ma kinitx osservata differenza klinikament relevanti fl- esponiment ta ’ lacosamide meta tqabbel il- farmakokinetika tiegħu f’ metabolizzanti estensivi (EMs, b ’ CYP2C19 funzjonali) u l- metabolizzanti deboli (PMs, li m’ għandhomx CYP2C19 funzjonali).
Pharmacokinetics in special patient groups Gender Clinical trials indicate that gender does not have a clinically significant influence on the plasma concentrations of lacosamide.
16 Sess Provi kliniċi juru li s- sess m’ għandux influenza klinikament sinifikanti fuq konċentrazzjoni fil- plażma ta ’ lacosamide.
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.
Indeboliment renali L’ AUC ta ’ lacosamide żdiedet b’ madwar 30% f’ pazjenti b’ indeboliment renali baxx u moderat u 60% f’ pazjenti b’ indeboliment renali sever u f’ pazjenti b’ mard renali fl- istadji ta ’ l- aħħar fejn hemm bżonn ta ’ emodijaliżi, meta mqabbel ma ’ pazjenti f’ saħħithom, iżda cmax ma ġiex affettwat.
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
F’ studji dwar it- tossiċita`, il- konċentrazzjoni fil- plażma ta ’ lacosamide li kien hemm kienu simili jew ħarira biss ogħla minn dawk osservati f’ pazjenti trattati b’ lacosamide, li tħalli marġini baxxi għal esponimemt fil- bniedem.
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.
Studju farmakoloġika ta ’ sigurta ’ b ’ teħid ġol- vina ta ’ lacosamide f’ klieb anastetiżżati wrew żiediet li jgħaddu fl- interval PR u d- dewmien tal- kumpless QRS u tnaqqis fil- pressjoni tad- demm li huma x’ aktarx minħabba azzjoni kardjodepressanti.
Studies in rats revealed that lacosamide and/ or its metabolites readily crossed the placental barrier.
17 Studji fil- firien juri li lacosamide u/ jew il- prodotti tal- metaboliżmu tiegħu jgħaddu faċilment minn ġol - plaċenta.
Tablet coat: polyvinyl alcohol polyethylene glycol 400, 3350 and 8000 talc soya-lecithin hypromellose titanium dioxide (E171) yellow iron oxide (E172)
Il- kisja tal- pillola: polyvinyl alcohol polyethylene glycol 400, 3350 u 8000 talc soya- lecithin hypromellose titanium dioxide (E171) yellow iron oxide (E172)
Packs of 14, 56 and 168 film-coated tablets.
Pakketti ta ’ 14, 56 u 168 pilloli miksija b’ rita
16 Not all pack sizes may be marketed.
Jista jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ EU/ 1/ 08/ 470/ 004- 006
Vimpat 150 mg film-coated tablets
Vimpat 150 mg pilloli miksija b’ rita
Each film-coated tablet contains 150 mg lacosamide.
Kull pillola miksija b’ rita fiha 150 mg lacosamide.
Each film-coated tablet contains 0.50 mg soya-lecithin.
Kull pillola miksija b’ rita fiha 0. 50 mg soya- lecithin.
Film-coated tablet Salmon, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 150’ on the other side.
Pillola miksija b’ rita ovali, kulur is- salamur, b ’ ‘ SP ’ imnaqqax fuq naħa waħda u ‘ 150 ’ fuq in- naħa l - oħra.
Use in elderly (over 65 years of age) No dose reduction is necessary in elderly patients.
20 Użu fl- anzjani (‘ l fuq minn 65 sena) M’ hemmx bżonn tnaqqis fid- doża f’ pazjenti anzjani.
Strong enzyme inducers such as rifampicin or St John´s wort (Hypericum perforatum) may moderately reduce the systemic exposure of lacosamide.
21 Mediċini li jindottaw l- enzimi b’ mod b’ saħħtu bħal rifampicin u St John’ s Wort (Hypericum perforatum) jistgħu jnaqqsu moderatament l- esponiment sistemiku ta ’ lacosamide.
Vimpat may have minor to moderate influence on the ability to drive and use machines.
22 Vimpat jista ’ jkollu effett minn żgħir għal moderat fuq il- ħila biex issuq u tħaddem magni.
20 moderate in intensity.
Dawn ħafna drabi kienu effetti ħfief għal moderati.
General disorders and administration site conditions Injury, poisoning and procedural complications
23 Għajja Korriment, avvelenament u komplikazzonijiet ta ’ xi proċedura
21 Pharmacotherapeutic group: other antiepileptics, ATC code:
Kategorija farmakoterapewtika: mediċini ta ’ kontra l- epilessija oħra, Kodiċi ATC:
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.
Vimpat 600 mg/ ġurnata kien muri effettiv fi 24 provi b’ terapija miżjuda kkontrollati, għalkemm l- effikaċja kienet simili għal 400 mg/ ġurnata u l - pazjenti x’ aktarx inqas ittolleraw din id- doża minħabba reazzjonijiet mhux mixtieqa relatati mas- CNS u dawk gastro- intestinali.
22 extensive metabolisers (EMs, with a functional CYP2C19) and poor metabolisers (PMs, lacking a functional CYP2C19).
Madanakollu, ma kinitx osservata differenza klinikament relevanti fl- esponiment ta ’ lacosamide meta tqabbel il- farmakokinetika tiegħu f’ metabolizzanti estensivi (EMs, b ’ CYP2C19 funzjonali) u l- metabolizzanti deboli (PMs, li m’ għandhomx CYP2C19 funzjonali).
Pharmacokinetics in special patient groups Gender Clinical trials indicate that gender does not have a clinically significant influence on the plasma concentrations of lacosamide.
25 Sess Provi kliniċi juru li s- sess m’ għandux influenza klinikament sinifikanti fuq konċentrazzjoni fil- plażma ta ’ lacosamide.