qanastek/EMEA-V3 huggingface dataset:
23 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.
26 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), red iron oxide (E172), black 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), red iron oxide (E172), black iron oxide (E172)
Packs of 14, 56 and 168 film-coated tablets (multipacks containing 3 packs of 56 tablets).
Pakketti ta ’ 14, 56 u 168 pilloli miksija b’ rita (pakketti multipli li fihom 3 pakketti ta ’ 56 għall- pilloli ta ’)
24 Not all pack sizes may be marketed.
Jista jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
UCB Pharma SA Allée de la Recherche 60 B-1070 Bruxelles Belgium
27 UCB Pharma SA Allée de la Recherche 60 B- 1070 Brussel Belġjum
Vimpat 200 mg film-coated tablets
Vimpat 200 mg pilloli miksija b’ rita
Each film-coated tablet contains 200 mg lacosamide.
Kull pillola miksija b’ rita fiha 200 mg lacosamide.
Each film-coated tablet contains 0.67 mg soya-lecithin.
Kull pillola miksija b’ rita fiha 0. 67 mg soya- lecithin.
Film-coated tablet Blue, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 200’ on the other side.
Pillola miksija b’ rita ovali, blu, b ’ ‘ SP ’ imnaqqax fuq naħa waħda u ‘ 200 ’ fuq in- naħa l- oħra.
Use in elderly (over 65 years of age) No dose reduction is necessary in elderly patients.
29 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.
30 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.
31 Vimpat jista ’ jkollu effett minn żgħir għal moderat fuq il- ħila biex issuq u tħaddem magni.
28 moderate in intensity.
Dawn ħafna drabi kienu effetti ħfief għal moderati.
General disorders and administration site conditions Injury, poisoning and procedural complications
32 Għajja Korriment, avvelenament u komplikazzonijiet ta ’ xi proċedura
29 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 33 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.
30 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.
34 Sess Provi kliniċi juru li s- sess m’ għandux influenza klinikament sinifikanti fuq konċentrazzjoni fil- plażma ta ’ lacosamide.
31 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.
35 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) indigo carmine aluminium lake (E132)
Il- kisja tal- pillola: polyvinyl alcohol polyethylene glycol 400, 3350 u 8000 talc soya- lecithin hypromellose titanium dioxide (E171) indigo carmine aluminium lake (E132)
32 Not all pack sizes may be marketed.
Jista jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
UCB Pharma SA Allée de la Recherche 60 B-1070 Bruxelles Belgium
36 UCB Pharma SA Allée de la Recherche 60 B- 1070 Brussel Belġjum
29 August 2008
29 ta ’ Awwissu
Vimpat 50 mg film-coated tablets Vimpat 100 mg film-coated tablets Vimpat 150 mg film-coated tablets Vimpat 200 mg film-coated tablets
Vimpat 50 mg pilloli miksija b’ rita Vimpat 100 mg pilloli miksija b’ rita Vimpat 150 mg pilloli miksija b’ rita Vimpat 200 mg pilloli miksija b’ rita
Pinkish, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 50’ on the other side.
Pillola miksija b’ rita ovali, tagħti fir- roża, b ’ ‘ SP ’ imnaqqxa fuq naħa waħda u ‘ 50 ’ fuq in- naħa l- oħra.
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.
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.
Blue, oval film-coated tablet debossed with ‘ SP’ on one side and ‘ 200’ on the other side.
Pillola miksija b’ rita ovali, blu, b ’ ‘ SP ’ imnaqqax fuq naħa waħda u ‘ 200 ’ fuq in- naħa l- oħra.
Vimpat treatment initiation pack contains 4 different packages (one for each tablet strength) with 14
38 Il- pakkett tal- bidu tat- trattament Vimpat fih 4 pakketti differenti (wieħed għal kull pillola ta ’ saħħa differenti) b’ 14 il- pillola kull wieħed, għall- ewwel 2 sa 4 ġimgħat ta ’ terapija skond ir- rispons u t - tollerabbilta` tal- pazjent.
The packages are marked with ‘ week 1 (2, 3 or 4 )’.
Il- pakketti huma mmarkati b ’ ‘ ġimgħa 1( 2, 3 jew 4) ’.
On the first day of treatment the patient starts with Vimpat 50 mg tablets twice a day.
Fl’ ewwel jum tat- trattament, il- pazjent jibda b ’ pilloli Vimpat 50 mg (darbtejn kuljum).
During the second week, the patient takes Vimpat 100 mg tablets twice a day.
Waqt it- tieni ġimgħa, il- pazjent jieħu pilloli Vimpat 100 mg (darbtejn kuljum).
Depending on response and tolerability, Vimpat 150 mg tablets may be taken twice a day during the third week and Vimpat 200 mg tablets twice a day during the fourth week.
Skond ir- rispons u t- tollerabbilta`, l- pilloli Vimpat 150 mg jistgħu jittieħdu darbtejn kuljum waqt it - tielet ġimgħa u l- pilloli Vimpat 200 mg darbtejn kuljum waqt ir- raba ’ ġimgħa.
Use in elderly (over 65 years of age) No dose reduction is necessary in elderly patients.
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 5.2).
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).
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 ’
The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lacosamide.
39 kontra l- epilessija juri żieda żgħira fir- riskju ta ’ ħsibijiet u mġieba suwiċidali.
Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.
Il- mekkaniżmu ta ’ dan ir- riskju mhux magħruf u d- dejta preżenti ma teskludix il- possibilta ’ ta ’ żieda fir- riskju b ’ lacosamide.
Patients (and caregivers of patients) should be advised to seek medical
Għalhekk il- pazjenti għandhom jiġu ċċekkjati għal sinjali ta ’ ħsibijiet u mġieba suwiċidali u għandu jitqies trattament xieraq.
35 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.
Strong enzyme inducers such as rifampicin or St John´s wort (Hypericum perforatum) may moderately reduce the systemic exposure of lacosamide.
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.
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 40 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.
36 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.
Vimpat may have minor to moderate influence on the ability to drive and use machines.
Vimpat jista ’ jkollu effett minn żgħir għal moderat fuq il- ħila biex issuq u tħaddem magni.
The most frequently reported adverse reactions with lacosamide treatment were dizziness, headache, nausea and diplopia.
L- iżjed effett mhux mixtieq li ġie rappurtat b’ lacosamide kienu sturdament, uġigħ ta ’ ras, dardir u diplowpja.
Balance disorder Coordination abnormal Memory impairment Cognitive disorder Somnolence Tremor Nystagmus
Taqlib tal- bilanċ Ko- ordinazzjoni abnormali Indeboliment tal - memorja Mard tal -
Eye disorders Ear and labyrinth disorders
41 konjizzjoni Ngħas Rogħda Nystagmus Mard ta ’ l- għajnejn Diplowpja Viżżjoni mċajpra Mard tal- widnejn u tas- sistema labirintika
Skin and subcutaneous tissue disorders
Rimettar Stitikezza Uġigħ ta ’ gas fl- istonku Mard tal- ġilda u tat- tessut ta ’ taħt il- ġilda
General disorders and administration site
Ħakk Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata
37 conditions Injury, poisoning and procedural complications
Diffikulta` fil- mixi Astenja Għajja Korriment, avvelenament u komplikazzonijiet ta ’ xi proċedura
Fatigue Fall Skin laceration
Waqgħa Feriti fil- ġilda
Pharmacotherapeutic group: other antiepileptics, ATC code:
N03AX18
N03AX18 The active substance, lacosamide (R-2-acetamido-N-benzyl-3-methoxypropionamide) is a functionalised amino acid.
42 Is- sustanza attiva, lacosamide (R- 2- acetamido- N- benzyl- 3- methoxypropionamide) huwa amino- aċidu funzjonalizzat.
Overall the
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.
38 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.
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.
43 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.
However, no 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).
In
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.
The body weight normalized difference is 26 and 23%, respectively.
Kienet
An increased variability in exposure was also observed.
44 osservata wkoll żieda fil- varjabbilita` ta ’ esponiment.
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 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.
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.
These transient changes started in the same concentration range as after maximum recommended clinical dosing.
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.
Tablet core: microcrystalline cellulose hydroxypropylcellulose hydroxypropylcellulose (low substituted) silica, colloidal, anhydrous crospovidone magnesium stearate 40 Tablet coat: polyvinyl alcohol polyethylene glycol 400, 3350 and 8000 talc soya-lecithin hypromellose titanium dioxide (E171)
Il- qalba tal- pillola: microcrystalline cellulose hydroxypropylcellulose hydroxypropylcellulose (low substituted) silica, colloidal, anhydrous crospovidone magnesium stearate
50 mg tablet: red iron oxide (E172), black iron oxide (E172), indigo carmine aluminium lake (E132) 100 mg tablet: yellow iron oxide (E172) 150 mg tablet: yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172) 200 mg tablet: indigo carmine aluminium lake (E132)
50 mg pillola: red iron oxide (E172), black iron oxide (E172), indigo carmine aluminium lake (E132) 100 mg pillola: yellow iron oxide (E172) 150 mg pillola: yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172) 200 mg pillola: indigo carmine aluminium lake (E132)
6.2 Incompatibilities
45 6. 2 Inkompatibilitajiet
The treatmenat initiation pack contains 4 cartons, each carton with 14 tablets of 50 mg, 100 mg, 150 mg and 200 mg
Il- pakkett tal- bidu tat- trattament fih 4 kaxxi, kull kaxxa b’ 14- il pillola ta’ 50 mg, 100 mg, 150 mg u 200 mg.
41 Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu/.
Informazzjoni dettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - mediċini (EMEA) http: // www. emea. europa. eu /.
Vimpat 15 mg/ ml syrup
Vimpat 15 mg/ ml mistura
Each ml of syrup contains 15 mg lacosamide.
Kull ml ta ’ mistura fih 15 mg lacosamide.
1 bottle of 200 ml contains 3000 mg lacosamide.
Flixkun wieħed ta ’ 200 ml fih 3000 mg lacosamide.
1 bottle of 465 ml contains 6975 mg lacosamide.
Flixkun wieħed ta ’ 465 ml fih 6975 mg lacosamide.
Each ml of Vimpat syrup contains 280 mg sorbitol (E420), 0.2 mg sodium propylparahydroxybenzoate (E217), 2.0 mg sodium methylparahydroxybenzoate (E219), 0.05 mg aspartame (E951) and 1.89 mg sodium.
Kull ml ta ’ mistura Vimpat fiha 280 mg sorbitol (E420), 0. 2 mg sodium propylparahydroxybenzoate (E217), 2. 0 mg sodium methylparahydroxybenzoate (E219), 0. 05 mg aspartame (E951), u 1. 89 mg sodju.
Syrup.
Mistura.
Clear solution, slightly yellow to yellow-brown in colour.
Soluzzjoni ċara, kemmxejn safranija għal safra fil- kannella.
Vimpat is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older.
Vimpat huwa indikat bħala terapija miżjuda fil- kura ta ’ aċċessjonijiet tat- tip ‘ partial- onset ’ kemm b’ ġeneralizzazzjoni sekondarja kif ukoll mingħajr, f’ pazjenti bl’ epilessija ta ’ 16 il- sena ‘ l fuq.
Vimpat syrup is provided with a measuring cup with graduation marks and instructions for use in the package leaflet.
Il- mistura Vimpat issibha b’ tazza tal- kejl b’ marki tal- kejl u struzzjonijiet għall- użu fil- fuljett ta ’ tagħrif.
The recommended starting dose is 50 mg twice a day which should be increased to an initial therapeutic dose of 100 mg twice a day after one week.
Id- doża rrikkmandata tal- bidu hija ta ’ 50 mg darbtejn kuljum, li għandha tiżdied għal doża terapewtika inizjali ta ’ 100 mg darbtejn kuljum wara ġimgħa.
Vimpat may be taken with or without food.
Id- doża ta ’ mantenament tista ’ tiġi miżjuda aktar, skond ir- rispons u t- tollerabbilta` b ’ 50 mg darbtejn kuljum kull ġimgħa, għal doża massima rrikkmandata ta ’ kuljum ta ’ 400 mg (200 mg darbtejn kuljum). Vimpat jista ’ jittieħed kemm ma ’ l- ikel kif ukoll mhux ma ’ l- ikel.
In accordance with current clinical practice, if Vimpat has to be discontinued, it is recommended this be done gradually (e. g. taper the daily dose by 200 mg/ week).
Jekk Vimpat ikollu jitwaqqaf, huwa rrikkmandat li dan isir gradwalment (eż. id- doża ta ’ kuljum titnaqqas b ’ 200 mg/ ġimgħa), skond il- prattika klinika kurrenti
For patients requiring haemodialysis a supplement of up to 50% of the divided daily dose directly after the end of haemodialysis is recommended.
Għal pazjenti li jkollhom bżonn id- dijaliżi tad- demm, huwa rrikkmandat suppliment ta ’ sa 50% tad- doża tal- ġurnata maqsuma eżatt wara d- dijaliżi tad- demm.
In all patients with renal impairment, the dose titration should be performed with caution (see section 5.2).
It- trattament tal- pazjenti bil- mard tal- kliewi fl- aħħar stadju għandu jsir b’ kawtela għaliex hemm biss ftit esperjenza klinika u hemm akkumulazzjoni ta ’ prodott tal- metaboliżmu (li m’ għandux attivita` farmakoloġika magħrufa). F’ kull pazjent b’ indeboliment tal- kliewi, it- titrazzjoni tad- doża għandha issir b’ kawtela (ara sezzjoni 5. 2).
The dose titration in these patients should be performed with caution considering co-existing renal
47 It- titrazzjoni tad- doża f’ dawn il- pazjenti għandha issir b’ kawtela, wara li jitqies ukoll xi indeboliment renali li jista ’ jkun hemm.
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).
L- esperjenza b’ lacosamide f’ pazjenti anzjani bl- epilessija hija limitata. F’ pazjenti anzjani, għandu jitqies it- tnaqqis fil- clearance tal- kliewi b’ żieda fil- livelli AUC assocjat ma’ żieda fl- eta` (ara ‘ Użu f’ pazjenti b’ indeboliment renali ’ hawn fuq u sezzjoni 5. 2).
Vimpat syrup contains sodium propylhydroxybenzoate (E217) and sodium methylhydroxybenzoate (E219), which may cause allergic reactions (possibly delayed).
Il- mistura Vimpat fiha sodium propylhydroxybenzoate (E217) u sodium methylhydroxybenzoate (E219), li jistgħu jikkawżaw reazzjonijiet allerġiċi (li jistgħu jseħħu wara).
It contains 3.7 g sorbitol (E420) per dose (200 mg lacosamide), corresponding to a calorific value of 9.7 kcal.
Din fiha 3. 7 g sorbitol (E420) kull doża (200 mg lacosamide), ekwivalenti għal valur kalorifiku ta ’ 9. 7 kcal.
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Pazjenti b ’ problemi rari ereditarji ta ’ intoleranza għal fructose, m’ għandhomx jieħdu din il- mediċina.
The syrup contains aspartame (E951), a source of phenylalanine, which may be harmful for people with phenylketonuria.
Il- mistura fiha aspartame (E951), li minnu jsir phenylalanine, li jista ’ jkun ta ’ ħsara għall- pazjenti b ’ phenylketonuria.
It contains 1.06 mmol (or 25.2 mg) sodium per dose (200 mg lacosamide).
Din fiha 1. 06 mmol (jew 25. 2 mg) sodju kull doża (200 mg lacosamide).
To be taken into consideration for patients on a controlled sodium diet.
Din għandha tittieħed f’ konsiderazzjoni f’ dawk il- pazjenti fuq dieta b’ kontrol tas- sodju.
Data generally suggest that lacosamide has a low interaction potential.
48 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,
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
In vitro studies indicate that lacosamide may be a weak inhibitor and inducer of CYP3A4.
Studji in vitro jindikaw li lacosamide jista ’ jkun inhibitur u indottur debboli ta ’ CYP3A4.
The clinical relevance of this is presently unknown.
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 u kontraċettivi orali fuq l- effett farmaċewtiku ma jindikawx 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.
Mediċini li jindottaw l- enzimi b’ mod b’ saħħtu bħal rifampicin u St John’ s Wort (Hypericum perforatum) jistgħu jnaqqsau 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.
Lacosamide plasma concentrations were not affected by carbamazepine and by 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 u l- 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 u phenobarbital, f’ dożi varji) naqset l- esponiment sistemiku totali ta ’ lacosamide b’ 25%.
Studies in animals did not indicate any teratogenic effects in rats or rabbits, but embroytoxicity 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).
Lacosamide should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus).
49 Lacosamide m’ għandux jintuża waqt it- tqala sakemm mhux ovvjament neċessarju (jekk il- benefiċċju għall- omm jiżboqq ir- riskju potenzjali għal fetu).
45 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Skin and subcutaneous tissue disorders
50 Mard tal- ġilda u tat - tessut ta ’ taħt il- ġilda
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.
46 There is limited clinical experience with lacosamide overdose in humans.
Hemm esperjenza klinika limitata b’ doża eċċessiva ta ’ lacosamide.
In non-clinical experiments lacosamide in combination with levetiracetam, carbamazepine, phenytoin, valproate, lamotrigine, topiramate or gabapentin showed synergistic or additive anticonvulsant effects.
Meta lacosamide
Thus, the 600 mg/ day dose is not recommended.
Għalhekk, id- doża ta ’ 600 mg/ ġurnata mhix irrikkmandat.
The maximum recommended dose is 400 mg/ day.
Id - doża massima rrikkmandata hija 400 mg/ ġurnata.
47 Distribution The volume of distribution is approximately 0.6 L/ kg.
Distribuzzjoni Il- volum ta ’ distribuzzjoni huwa madwar 0. 6 L/ kg.
The major compounds excreted in urine are unchanged lacosamide (approximately 40% of the dose) and its O-desmethyl metabolite less than 30%.
Il- metaboliżmu ta ’ lacosamide ma kienx kompletament ikkaratterizzat. 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%).
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.
Il- half- life ta ’
The elimination half-life of the unchanged drug is approximately 13 hours.
52 eliminazzjoni tal- mediċina mhux mibdula kienet ta ’ madwar 13- il siegħa.
Therefore dosage supplementation following haemodialysis is recommended (see section 4.2).
Għalhekk huwa rrikkmandat suppliment fid- dożaġġ wara l- emodijaliżi (ara sezzjoni 4. 2).
The exposure of the O-desmethyl metabolite was several-fold increased in patients with moderate and severe renal impairment.
L- esponiment tal – prodott tal- metaboliżmu O- desmethyl kien miżjud b’ diversi drabi f’ pazjenti b’ indeboliment moderat jew sever.
In absence of haemodialysis in patients with endstage renal disease, the levels were increased and continuously rising during the 24-hour sampling.
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.
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.
48 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.
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.
53 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.
glycerol (E422) carmellose sodium sorbitol liquid (crystallizing) (E420) polyethylene glycol 4000 sodium chloride citric acid, anhydrous acesulfame potassium (E950) sodium propylparahydroxybenzoate (E217) sodium methylparahydroxybenzoate (E219) strawberry flavour (contains propylene glycol, maltol) masking flavour (contains propylene glycol, aspartame (E951), acesulfame potassium (E950), maltol, deionised water) purified water
glycerol (E422) carmellose sodium sorbitol liquid (crystallizing) (E420) polyethylene glycol 4000 sodium chloride citric acid, anhydrous acesulfame potassium (E950) sodium propylparahydroxybenzoate (E217) sodium methylparahydroxybenzoate (E219) togħma ta ’ frawli (fih propylene glycol maltol, deionised water) masking flavour (fih propylene glycol, aspartame (E951), acesulfame potassium (E950), maltol deionised water) ilma purifikat
49 2 years After first opening:
Wara l- ewwel li jinfetaħ:
Do not store above 30°C.
Taħżinx ‘ l fuq minn 30°C.
200 ml and 465 ml amber type III glass or polyethylene terephthalate (PET) bottles with a polypropylene screw cap and a measuring cup.
Flixken ta ’ 200 ml u 465 ml tal- ħġieġ tat- tip III ta ’ kulur ambra jew flixken tal- polyethylene b’ tap bil - kamin tal- polypropylene u tapp tal- kejl.
UCB Pharma SA Allée de la Recherche 60 B-1070 Bruxelles Belgium
54 UCB Pharma SA Allée de la Recherche 60 B- 1070 Brussel Belġjum
MARKETING AUTHORISATION NUMBER(S)
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ EU/ 1/ 08/ 470/ 014- 015
Vimpat 10 mg/ ml solution for infusion
Vimpat 10 mg/ ml soluzzjoni għall- infużjoni
Each ml of solution for infusion contains 10 mg lacosamide.
Kull ml ta ’ soluzzjoni għall- infużjoni fih 10 mg ta’ lacosamide.
1 vial of 20 ml solution for infusion contains 200 mg lacosamide.
Fjala waħda ta ’ 20 ml ta ’ soluzzjoni għall- infużjoni fiha 200 mg ta’ lacosamide.
Each ml of solution for infusion contains includes 2.99 mg sodium.
Kull ml ta ’ soluzzjoni għall- infużjoni jinkludi 2. 99 mg sodju.
For a full list of excipients, see section 6.1
Għal lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Clear, colourless solution.
Soluzzjoni ċara mingħajr kulur.
Vimpat solution for infusion is an alternative for patients when oral administration is temporarily not feasible.
Is- soluzzjoni għall- infużjoni hija alternattiva għal pazjenti meta ma jkunx possibli li jieħdu il- mediċina mill- ħalq.
Vimpat must be administered twice a day.
Vimpat għandu jingħata darbtejn kuljum..
Depending on response and tolerability, the maintenance dose can be further increased by 50 mg twice a day every week, to a maximum recommended daily dose of 400 mg (200 mg twice a day).
Id - doża ta ’ mantenament tista ’ tiġi miżjuda aktar, skond ir- rispons u t- tollerabbilta`, b ’ 50 mg darbtejn kuljum kull ġimgħa, għal doża massima rrikkmandata ta ’ kuljum ta ’ 400 mg (200 mg darbtejn kuljum).
Vimpat therapy can be initiated with either oral or i. v. administration.
It- terapija Vimpat tista ’ tibda tittieħed mill- ħalq jew minn ġol- vina.
The solution for infusion is infused over a period of 15 to 60 minutes twice daily.
Is- soluzzjoni għall- infużjoni tingħata fuq perjodu ta ’ 15 sa 60 minuti darbtejn kuljum.
Vimpat solution for infusion can be administered i. v. without further dilution.
Is- soluzzjoni Vimpat għall- infużjoni jista ’ jingħata minn ġol- vina mingħajr ma ’ jiġi dilwit aktar.
Conversion to or from oral and i. v. administration can be done directly without titration.
Wieħed jista ’ jaqleb minn teħid orali għal ġol- vina jew l- kontra, mingħajr titrazzjoni.
The total daily dose and twice daily administration should be maintained.
Trid tibqa ’ l- istess id- doża totali ta ’ kuljum u t- teħid ta’ darbtejn kuljum.
There is experience with twice daily infusions of Vimpat up to 5 days.
Hemm esperjenza b’ infużjonijiet ta ’ Vimpat ta ’ darbtejn kuljum sa 5 tijiem.
For patients requiring haemodialysis a supplement of up to 50% of the divided daily dose directly after the end of haemodialysis is recommended.
Għal pazjenti li jkollhom bżonn id- dijaliżi tad- demm, huwa rrikkmandat suppliment ta ’ sa 50% tad- doża tal- ġurnata maqsuma eżatt wara d- dijaliżi tad- demm. It- trattament tal- pazjenti bil- mard tal- kliewi fl- aħħar stadju għandu jsir b’ kawtela għaliex hemm biss ftit esperjenza klinika u hemm akkumulazzjoni ta ’ prodott tal -
In all patients with renal impairment, the dose titration should be performed with caution (see section 5.2).
56 metaboliżmu (li m’ għandux attivita` farmakoloġika magħrufa). F’ kull pazjent b’ indeboliment tal - kliewi, it- titrazzjoni tad- doża għandha issir b’ kawtela (ara sezzjoni 5. 2).
51 Use in patients with hepatic impairment No dose adjustment is needed for patients with mild to moderate hepatic impairment.
Użu f’ pazjenti b’ indeboliment tal- fwied M’ hemmx bżonn aġġustament f’ pazjenti b’ indeboliment ħafif jew moderat tal- fwied.
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).
F’ pazjenti anzjani, għandu jitqies it- tnaqqis fil- clearance tal- kliewi b’ żieda fil- livelli AUC assocjat ma’ żieda fl- eta` (ara ‘ Użu f’ pazjenti b’ indeboliment renali ’ hawn fuq u sezzjoni 5. 2).
This medicinal product contains 2.6 mmol (or 59.8 mg) sodium per vial.
Dan il- prodott mediċinali fih 2. 6 mmol (jew 59. 8 mg) sodju f’ kull fjala.
To be taken into consideration for patients on a controlled sodium diet.
Din għandha tiġi meqjusa f’ pazjenti fuq dieta ta ’ sodju kontrollat.
Data generally suggest that lacosamide has a low interaction potential.
57 Id- dejta ġeneralment jissuġġerixxi li lacosamide għandu potenzjal baxx għal interazzjoni bejn mediċina u oħra.
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
Lacosamide ma jinibixxix jew ma jindottax l- enżim CYP2C19 in vivo.
An interaction study with carbamazepine does not indicate a marked inhibitory effect of lacosamide on CYP3A4 catalysed metabolism at therapeutic doses.
Studji dwar l- effett ta ’ b’ carbamazepine u kontraċettivi orali fuq l- effett farmaċewtiku ma jindikawx effett inibitorju notevoli ta ’ lacosamide fuq il- metaboliżmu katalizzat b ’ CYP3A4 f’ dożi terapewtiċi.
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 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..
Omeprazole 40 mg q. d. increased the AUC of lacosamide by 19%.
Omeprazole40 mg q. d. żied l- AUC ta ’ lacosamide b ’ 19%.
Lacosamide has a low protein binding of less than 15%.
M’ hemmx tagħrif fuq l- effett ta ’ lacosamide ma ’ l- alkoħol. Lacosamide jeħel mal- protejini tad- demm b’ rata baxxa ta ’ 15%.
Studies in animals did not indicate any teratogenic effects in rats or rabbits, but embryotoxicity 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).
Lactation It is unknown whether lacosamide is excreted in human breast milk.
58 Treddiegħ Mhux magħruf jekk lacosamide jinħeriex fil- ħalib ta’ l- omm fil- bniedem.
Vimpat may have minor to moderate influence on the ability to drive and use machines.
Vimpat jista ’ effett minn żgħir għal moderat fuq il- ħila biex issuq u tħaddem magni..
General disorders and administration site conditions Injury, poisoning and procedural complications
59 kondizzjonijiet ta ’ mnejn jingħata Korriment, avvelenament u komplikazzonijiet ta ’ xi proċedura
Gait disturbance Asthenia Fatigue Fall Skin laceration
Astenja Għajja Waqgħa Feriti fil- ġilda
54 There is limited clinical experience with lacosamide overdose in humans.
Hemm esperjenza klinika limitata b’ doża eċċessiva ta ’ lacosamide.
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 u carbamazepine, phenytoin, valproate, lamotrigine, topiramide jew gabapentin wera effetti ta ’ kontra l- epilessija purament sinerġistiċi b’ effetti mhux mixtieqa tal- moviment li ma jiżdiedux b’ mod addittiv.
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.
60 Esperjenza klinika L- effikaċja ta ’ Vimpat bħala terapija aġġuntiva fid- dożi rrikkmandati (200 mg/ ġurnata, 400 mg/ ġurnata, 600 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 irrikkmandat.
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 mhux kontrollati tat- tip partial onset kemm bi kif ukoll mingħajr ġeneralizzazzjoni sekondarja.
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.
Absorption After i. v. administration, Cmax is reached at the end of infusion.
Assorbiment Wara t- teħid minn ġol- vina, C max jintlaħaq fl- aħħar ta ’ l- infużjoni.
(50-300 mg) administration.
Il- konċentrazzjoni tal- plażma tiżdied proporzjonalment mad- doża war li jittieħed mill- ħalq (100- 800 mg) u minn ġol- vina (50- 300 mg).
Lacosamide is less than 15% bound to plasma
Lacosamide huwa marbut b ’ inqas minn 15% mal - proteini fil- plażma.
The metabolism of lacosamide has not been completely characterised.
Il- metaboliżmu ta ’ lacosamide ma kienx kompletament karatterizzata.
CYP2C19 is mainly responsible for the formation of the O-desmethyl metabolite.
CYP2C19 huwa riponsabli prinċipalment għall- formazzjoni tal- prodott tal- metaboliżmu O- desmethyl.
However, no 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).
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
Lacosamide is effectively removed from plasma by haemodialysis.
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. Lacosamide huwa effettivament imneħħi mill- plażma b’ emodijaliżi.
Therefore dosage supplementation following haemodialysis is recommended (see section 4.2).
Għalhekk huwa rrikkmandat suppliment fid- dożaġġ wara l - emodijaliżi (ara sezzjoni 4. 2).).
In absence of haemodialysis in patients with endstage renal disease, the levels were increased and continuously rising during the 24-hour sampling.
Meta ma kienx hemm emodijaliżi f’ pazjenti b’ mard tal- kliewi fl- aħħar fażi, il- livelli kienu ogħla u żiedu kontinwament waqt li ttieħdu s - samples 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.
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
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.
Apart from the hypertrophy of hepatocytes, no other histopathologic changes were observed.
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
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.
62 b’ dożi tossiċi fl- omm fil- firien li jikkorrespondu għal livelli ta ’ esponiment sistemiċi simili għal esponiment kliniku mistenni.
water for injection sodium chloride hydrochloric acid (for pH adjustment)
Ilma għall- injezzjoni Sodium chloride Hydrochloric acid (għall- aġġustament tal- pH)
Chemical and physical in-use stability has been demonstrated for 24 hours at temperatures up to 25° C for product mixed with the diluents mentioned in 6.6.
L- istabbilta`kimika u fiżika waqt l- użu kien muri għal 24 siegħa f’ temperaturi sa 25ºC għal prodotti mħallta ma ’ diwenti msemmija f ’ 6. 6.
From a microbiological point of view, the product should be used immediately.
Mill- lat mikrobijoloġiku, il- prodotti għandu jintuża immedjatament.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Jekk ma jintużax immedjatament, iż- żmien li jagħmel maħżun waqt l- użu u l- kondizzjonijiet qabel l- użu huma r- responsabilta` ta ’ minn juża l- mediċina u m’ għandiex tkun itwal minn 24 siegħa f ’ 2 sa 8°C, sakemm id- dilwizzjoni ma sarx f’ kondizzjonijiet assettiċi kontrollati u kkonfermat
57 Do not store above 25°C.
Taħżinx ‘ l fuq minn 25°C.
1x20 ml colourless type I glass vial with a chlorobutyl rubber closure coated with a fluoropolymer.
1x20 ml fjala tal- ħġieġ tat- tip I, bla kulur, b ’ tap tal- gomma chlorobutyl miksi b’ fluoropolymer.
This medicinal product is for single use only, any unused solution should be discarded.
Dan il- prodott huwa għal użu ta ’ darba biss, u kull soluzzjoni li ma tintużax trid tintrema.
Product with particulate matter or discolouration should not be used.
Prodott bil- frak jew diskolorazzjoni m’ għandux jintuża.
Vimpat solution for infusion was found to be physically compatible and chemically stable when mixed with the following diluents for at least 24 hours and stored in glass or PVC bags at temperatures up to 25°C.
Dilwenti:
Diluents: sodium chloride 9 mg/ ml (0.9%) solution for injection glucose 50 mg/ ml (5%) solution for injection lactated Ringer’ s solution for injection.
Sodium chloride 9 mg/ ml (0. 9%) soluzzjoni għall- injezzjoni Dextrose 50 mg/ ml (5%) soluzzjoni għall- injezzjoni soluzzjoni għall- injezzjoni lactated Ringer’ s
UCB Pharma SA Allée de la Recherche 60 B-1070 Bruxelles Belgium
63 UCB Pharma SA Allée de la Recherche 60 B- 1070 Brussel Belġjum
58 ANNEX II
64 ANNESS II
10 D-40789 Monheim Germany
10 D- 40789 Monheim Ġermanja
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 5 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema tal - Farmakoviġilanza Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq irid jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta f’ verzjoni 5 preżentata fis- Sezzjoni 1. 8. 1 tal- Awtorizzazzjoni ta ’ Tqegħid fis- Suq, tkun implimentata u taħdem qabel ma, u waqt li l- prodott jibda jinbiegħ.