qanastek/EMEA-V3 huggingface dataset:
Neither levetiracetam nor its primary metabolite are significantly bound to plasma proteins (< 10%).
La levetiracetam u lanqas il- prodott ewlieni tal- metaboliżmu ma jeħlu wisq mal- proteini tal- plażma (< 10%).
The volume of distribution of levetiracetam is approximately 0.5 to 0.7 l/ kg, a value close to the total body water volume.
Dan il- valur huwa qrib il- volum totali ta ’ l- ilma fil- ġisem.
Biotransformation
Bijotrasformazzjoni
Levetiracetam is not extensively metabolised in humans.
Levetiracetam mhux metabolizzat estensivament fil- bniedem.
Production of the primary metabolite, ucb L057, is not supported by liver cytochrome P450 isoforms.
Il- mod prinċipali kif jiġi metabolizzat (24% tad- doża) huwa permezz ta 'idroliżi tal- grupp aċetamajd. L- iżoformi taċ- ċitokromju P450 fil - fwied ma jgħinux il- produzzjoni ta' ucb L057, li huwa l- prodott ewlieni tal- metaboliżmu.
Hydrolysis of the acetamide group was measurable in a large number of tissues including blood cells.
L- idroliżi tal- grupp aċetamajd seta 'jiġi mkejjel f' numru kbir ta' tessuti fosthom iċ- ċelloli tad- demm.
The metabolite ucb L057 is pharmacologically inactive.
Ucb L057 mhuwiex attiv farmakoloġikament.
Two minor metabolites were also identified.
Kienu wkoll identifikati żewġ prodotti tal- metaboliżmu inqas importanti.
One was obtained by hydroxylation of the pyrrolidone ring (1.6% of the dose) and the other one by opening of the pyrrolidone ring (0.9% of the dose).
Wieħed isir permezz ta ’ l - idroliżi taċ- ċirku ta ’ pyrrolidone (0. 9% tad- doża) u l- ieħor isir permezz tal- ftuħ taċ- ċirku ta ’ pyrrolidone.
Other unidentified components accounted only for 0.6% of the dose.
Komponenti oħrajn li ma ġewx identifikati jagħmlu biss 0. 6% mid- doża kollha.
No enantiomeric interconversion was evidenced in vivo for either levetiracetam or its primary metabolite.
Ma kien hemm ebda evidenza in vivo li kien hemm xi tibdil enantjomeriku kemm f 'levetiracetam kif ukoll fil- prodott ewlieni tal- metaboliżmu.
In vitro, levetiracetam and its primary metabolite have been shown not to inhibit the major human liver cytochrome P450 isoforms (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyl transferase (UGT1A1 AND UGT1A6]) and epoxide hydroxylase activities.
In vitro, kemm levetiracetam u kemm il- prodott ewlieni tal- metabolożmu ma fixklux l- iżoformi taċ - ċitokromju P450 fil- fwied (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 u 1A2), glucuronyl transferase (UGT1A1 u UGT1A6) u l- attivitajiet ta ’ l- epoxide hydroxylase.
In addition, levetiracetam does not affect the in vitro glucuronidation of valproic acid.
Levetiracetam m’ għandu ebda effett ukoll fuq il- glukuronidazzjoni ta ’ valproic acid in vitro.
In human hepatocytes in culture, levetiracetam had little or no effect on CYP1A2, SULT1E1 or UGT1A1.
Levitiracetam kellu ftit jew ebda effett fuq CYP1A2, SULT1E1 jew UGT1A1 f' kolturi ta 'ċelloli tal- fwied umani.
Levetiracetam caused mild induction of CYP2B6 and CYP3A4.
Levitiracetam ikkawża induzzjoni ħafifa ta ’ CYP2B6 u CYP3A4.
The in vitro data and in vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme induction is expected in vivo.
Tagħrif in vitro u tagħrif dwar l- interazzjoni in vivo fuq kontraċettivi orali, digoxin u warfarina jindika li mhux mistenni li jkun hemm induzzjoni sinifikanti ta ’ l- enżimi.
Therefore, the interaction of Keppra with other substances, or vice versa, is unlikely.
Għalhekk hija improbabbli li Keppra ma jaqbilx ma 'sustanzi oħra, u viċe versa.
Elimination 10 The plasma half-life in adults was 7±1 hours and did not vary either with dose, route of administration or repeated administration.
Din ir- rata ma titbiddilx kemm jekk titbiddel id- doża, kemm jekk jitbiddel il- metodu kif jingħata levetiracetam, kif ukoll jekk jingħata ripetutament.
The mean total body clearance was 0.96 ml/ min/ kg.
Ir- rata medja li biha jitneħħa għall- kollox kienet ta '0. 96 ml/ min/ kg.
The major route of excretion was via urine, accounting for a mean 95% of the dose (approximately 93% of the dose was excreted within 48 hours).
Kwazi 93% tad- doża kienet mneħħija f '48 siegħa.
Excretion via faeces accounted for only 0.3% of the dose.
0. 3% tad- doża biss titneħħa ġo l- ippurgar.
The cumulative urinary excretion of levetiracetam and its primary metabolite accounted for 66% and 24% of the dose, respectively during the first 48 hours.
Fl- ewwel 48 siegħa, it- tneħħija kumulattiva ta 'levetiracetam fl- awrina kienet ta' 66% tad- doża, iżda dik tal- prodott ewlieni tal- metaboliżmu kienet tagħmel biss 24% tad- doża.
The renal clearance of levetiracetam and ucb L057 is 0.6 and 4.2 ml/ min/ kg respectively indicating that levetiracetam is excreted by glomerular filtration with subsequent tubular reabsorption and that the primary metabolite is also excreted by active tubular secretion in addition to glomerular filtration.
Dan juri li levetiracetam jitneħħa permezz ta 'filtrazzjoni glomerulari u wara jerġa' jiġi assorbit mit- tubules, u li ucb L057 jitneħħa permezz ta 'filtrazzjoni glomerulari kif ukoll permezz ta' passaġġ attiv mit- tubules tal- kliewi.
Levetiracetam elimination is correlated to creatinine clearance.
It- tneħħija ta 'levetiracetam tixbah dik tal- krejatinina.
In the elderly, the half-life is increased by about 40% (10 to 11 hours).
10 Fl- anzjani, il- half life ta 'levetiracetam fid- demm tiżdied b’ 40% (10 sa 11 il- siegħa).
This is related to the decrease in renal function in this population (see section 4.2).
(ara sezzjoni 4. 2 “ Pożoloġija ”).
Children (4 to 12 years)
Tfal (4 sa 12- il sena)
Following single oral dose administration (20 mg/ kg) to epileptic children (6 to 12 years), the half-life of levetiracetam was 6.0 hours.
Wara li ngħatat doża orali waħda li tammonta għal 20 mg/ kg lil tfal bl- epilessija (6 sa 12 il- sena), il - half life ta ’ levetiracetam kienet 6. 0 sigħat.
The apparent body weight adjusted clearance was approximately 30% higher than in epileptic adults.
It- tneħħija ta 'levetiracetam fit- tfal kienet 30% iżjed minn dik f' adulti li jbatu mill- epilessija meta ġiet ikkonsidrata d- differenza fil- piż.
Following repeated oral dose administration (20 to 60 mg/ kg/ day) to epileptic children (4 to 12 years), levetiracetam was rapidly absorbed.
Levetiracetam kien assorbit malajr f’ tfal b’ epilessija (4 sa 12 il- sena) wara li ingħataw doża orali repetuta (20 sa 60 mg/ kg/ day).
Peak plasma concentration was observed 0.5 to 1.0 hour after dosing.
Il- konċentrazzjoni massima fil- plażma kienu osservati 0. 5 sa 1. 0 siegħa wara d- doża.
Linear and dose proportional increases were observed for peak plasma concentrations and area under the curve.
Żiediet linejari u proporzjonali għad- doża kienu osservati bil - konċentrazzjonijiet massimi fil- plażma u l- erja taħt il- kurva.
The elimination half-life was approximately 5 hours.
Il- half- life ta ’ eliminazzjoni kien bejn wieħed u ieħor 5 siegħat.
The apparent body clearance was 1.1 ml/ min/ kg.
Il- clearance fil- ġisem deher li kien 1. 1 ml/ min/ kg.
Infants and children (1 month to 4 years)
Trabi u tfal (xahar sa 4 snin)
Following single dose administration (20 mg/ kg) of a 100 mg/ ml oral solution to epileptic children (1 month to 4 years), levetiracetam was rapidly absorbed and peak plasma concentrations were observed approximately 1 hour after dosing.
Wara li ngħatat doża waħda (20 mg/ kg) ta ’ 100 mg/ ml soluzzjoni orali lil tfal epilettiċi (xahar sa 4 snin), levetiracetam kien assorbit malajr u l- konċentrazzjonijiet massimi fil- plażma kienu osservati bejn wieħed u ieħor siegħa wara d- doża.
The pharmacokinetic results indicated that half-life was shorter (5.3 h) than for adults (7.2 h) and apparent clearance was faster (1.5 ml/ min/ kg) than for adults (0.96 ml/ min/ kg).
Ir- riżultati farmakokinetiċi wrew li l- half- life kien iqsar (5. 3 h) minn dak fl- adulti (7. 2 h) u l- clearance li deher kien iżjed mgħaġġel (1. 5 ml/ min/ kg) minn dak fl - adulti (0. 96ml/ min/ kg).
Renal impairment
Indeboliment tal- kliewi
The apparent body clearance of both levetiracetam and of its primary metabolite is correlated to the creatinine clearance.
It- tneħħija kemm ta 'levetiracetam u kemm tal- prodott ewlieni tal- metaboliżmu tixbah dik tal - krejatinina.
It is therefore recommended to adjust the maintenance daily dose of Keppra, based on creatinine clearance in patients with moderate and severe renal impairment (see section 4.2).
Għalhekk hija rrikkmandata li f 'pazjenti li jkollhom indeboliment moderat u sever fil - kliewi, id- doża ta' Keppra tkun maħduma fuq ir- rata li biha titheħħa l- krejatinina (ara sezzjoni 4. 2).
In anuric end-stage renal disease adult subjects the half-life was approximately 25 and 3.1 hours during interdialytic and intradialytic periods, respectively.
F 'pazjenti adulti li kienu fl- aħħar stadji tal- marda tal- kliewi u fejn ma' jkunu qed jgħaddu xejn mill - kliewi, il- half life ta 'levetiracetam fid- demm kienet 25 siegħa waqt perijodi ta' bejn id- dijaliżi u 3. 1 sigħat fil- perijodi waqt li tkun qed issir id- dijaliżi.
The fractional removal of levetiracetam was 51% during a typical 4-hour dialysis session.
It- tneħħija frazzjonali kienet ta’ 51% ta 'levetiracetam waqt sezzjoni tad- dijaliżi tipika li damet 4 sigħat.
In subjects with mild and moderate hepatic impairment, there was no relevant modification of the clearance of levetiracetam.
M' hemmx differenzi fir- rata ta 'tneħħija ta' levetiracetam f 'pazjenti b' mard hafif u moderat tal- fwied.
In most subjects with severe hepatic impairment, the clearance of levetiracetam was reduced by more than 50% due to a concomitant renal impairment (see section 4.2).
Fil- biċċa l- kbira tal- pazjenti b 'mard serju tal- fwied din kienet imnaqqsa b' iżjed minn 50% minħabba ħsara wkoll fil- kliewi (ara sezzjoni 4. 2).
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity and carcinogenicity.
Tagħrif mhux fuq l- użu kliniku meħud minn studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku fuq il- ġeni, u riskju ta ’ kanċer, ma ’ turi l- ebda periklu speċjali għall- bnedmin.
Adverse effects not observed in clinical studies but seen in the rat and to a lesser extent in the mouse at exposure levels similar to human exposure levels and with possible relevance for clinical use were liver changes, indicating an adaptive response such as increased weight and centrilobular hypertrophy, fatty infiltration and increased liver enzymes in plasma.
Dawk l- effetti li jista 'jkollhom rilevanza fl- użu kliniku huma: bidliet fil- fwied li jindikaw rejazzjonijiet bħal żieda fil- piż u ipertrofija ċentrilobulari, żieda fil- livell tax- xaħam u żieda fl- enżimi tal- fwied fil- plażma.
In reproductive toxicity studies in the rat, levetiracetam induced developmental toxicity (increase in skeletal variations/ minor anomalies, retarded growth, increased pup mortality) at exposure levels similar to or greater than the human exposure.
Fi studji ta 'tossiċità riproduttiva fil- far, kien hemm tossiċità ta ’ l- iżvilupp bl- użu ta' levetiracetam (żieda fil- varjazzjonijiet skeletali / anomaliji minuri, tkabbir iżjed bil- mod, u żieda fir- rata tal- mewt tal - wild) wara espożizzjonijiet simili jew aktar għolja minn tal- bniedem.
In the rabbit foetal effects (embryonic death, increased skeletal anomalies, and increased malformations) were observed in the presence of maternal toxicity.
Fil- fenek, effetti fuq il- fetu (mewt ta ’ l- embriju, żieda fl- anomaliji skeletali u żieda fil- malformazzjonijiet) ġew osservati meta kien hemm tossiċità fl- omm.
The systemic exposure at the observed no effect level in the rabbit was about 4 to 5 times the human exposure.
Ebda effett ma kien osservat fil- fenek meta l- livell fid- demm kien minn 4 sa 5 darbiet ta 'dak fil- bniedem.
Sodium croscarmellose Macrogol 6000 Colloidal anhydrous silica Magnesium stearate
Sodium croscarmellose Macrogol 6000 Colloidal anhydrous silica Magnesium stearate
Film-coating Opadry 85F20694:
Il- kisja tar- rita Opadry 85F20694:
Polyvinyl alcohol-part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc Indigo carmine aluminium lake (E132)
Polyvinyl alcohol- part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc
6.2 Incompatibilities
6. 2 Inkompatibiltajiet
6.4 Special precautions for storage
6. 4 Prekawzjonijiet dwar ħażna speċjali
No special precautions for storage.
L- ebda ħtiġijiet speċjali għal ħażna.
Keppra 250 mg film-coated tablets are packaged in aluminium/ PVC blisters placed into cardboard boxes containing 20, 30, 50, 60, 100 and 200 film-coated tablets.
Keppra 250 mg pilloli miksija b' rita huma ippakkjati f' folji ta ’ l- aluminju/ PVC u mqegħda f 'kaxxi tal - kartun ta' 20, 30, 50, 60, 100 u 200 pillola miksija b' rita.
Allée de la Recherche 60 B-1070 Bruxelles Belgium
UCB Pharma SA Allée de la Recherche 60 B- 1070 Bruxelles Belġju
Date of first authorisation:
Data l- ewwel awtorizzazzjoni:
29 September 2000 Date of last renewal:
29 ta 'Settembru, 2000 Data ta ’ l- aħħar tiġdid ta ’ l- awtorizzazzjoni:
08 July 2005
08 ta ’ Lulju, 2005
Keppra 500 mg film-coated tablets.
Keppra 500 mg pilloli miksija b' rita.
Each film-coated tablet contains 500 mg levetiracetam.
Kull pillola miksija b' rita fiha 500 mg levetiracetam.
Yellow, oblong, scored and debossed with the code “ ucb” and “ 500” on one side.
Safra, tawwalija, maqtuha minn nofs u mnaqqxa bil- kodiċi “ ucb ” u ” 500 ” fuq naħa waħda.
14 Adjustment of the dose is recommended in elderly patients with compromised renal function (see “ Patients with renal impairment ” below).
14 (ara “ Pazjenti b’ indeboliment tal- kliewi ” hawn taħt).
30 mg/ kg twice daily
30 mg/ kg darbtejn kuljum
15 kg (1) 20 kg (1) 25 kg From 50 kg (2) (1)
15 kg (1) 20 kg (1) 25 kg Minn 50 kg (2) (1)
150 mg twice daily 200 mg twice daily 250 mg twice daily 500 mg twice daily
150 mg darbtejn kuljum 200 mg darbtejn kuljum 250 mg darbtejn kuljum 500 mg darbtejn kuljum
450 mg twice daily 600 mg twice daily 750 mg twice daily 1500 mg twice daily
450 mg darbtejn kuljum 600 mg darbtejn kuljum 750 mg darbtejn kuljum 1500 mg darbtejn kuljum
[140-age (years)] x weight (kg) CLcr (ml/ min) = ----------------------------------------- 72 x serum creatinine (mg/ dl)
[140 - eta` (snin)] x piż (kg) Clcr( ml/ min) =
(x 0.85 for women)
------------------------------------------------ (x 0. 85 għan- nisa) 72 x livell ta 'krejatinina fis- serum (mg/ dl)
CLcr (ml/ min) CLcr (ml/ min/ 1.73 m2) = ---------------------------- x 1.73 BSA subject (m2)
CLcr (ml/ min) CLcr (ml/ min/ 1. 73 m2) = ---------------------------- x 1. 73 BSA pazjent (m2)
15 Dosing adjustment for adult patients with impaired renal function
15 Regolar tad- doża f' pazjenti adulti bi ħsara fil- kliewi
16 Therefore patients should be monitored for signs of depression and/ or suicidal ideation and behaviours and appropriate treatment should be considered.
Għalhekk il- pazjenti għandhom jiġu ċċekkjati għal sinjali ta ’ depressjoni u/ jew ħsibijiet u mġieba suwiċidali u għandu jitqies trattament xieraq.
4.5 Interaction with other medicinal products and other forms of interaction
16 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
17 No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
Due to possible different individual sensitivity, some patients might experience somnolence or other central nervous system related symptoms, especially at the beginning of treatment or following a dose increase.
Speċjalment fil- bidu tat - trattament jew wara żieda fid- doża, xi pazjenti li possibilment ikunu iżjed sensittivi, jistgħu jitħeddlu jew iħossu sintomi oħrajn relatati mas- sistema nervuża ċentrali.
4.8 Undesirable effects
17 4. 8 Effetti mhux mixtieqa
Very common: asthenia/ fatigue.
Komuni ħafna: astenja/ għajja.
18 Common: amnesia, ataxia, convulsion, dizziness, headache, hyperkinesia, tremor, balance disorder, disturbance in attention, memory impairment.
Komuni ħafna: ħedla Komuni: amneżija, ataksja (movimenti mhux ko- ordinati), aċċessjoni, sturdament, uġigħ ta 'ras, iperkineżja, rogħda, mard tal- bilanċ, disturbi fl- attenzjoni u telf ta ’ memorja.
Common: agitation, depression, emotional lability / mood swings, hostility/ aggression, insomnia, nervousness/ irritability, personality disorders, thinking abnormal Post-marketing experience: abnormal behaviour, anger, anxiety, confusion, hallucination, psychotic disorder, suicide, suicide attempt and suicidal ideation
Komuni: aġitazzjoni, depressjoni, disturbi emozzjonali, tibdil fil- burdata, ostilità / aggressjoni, nuqqas ta 'rqad, nervożita` / irritabilita`, disturbi fil- personalita`, ħsieb mhux normali Esperjenza wara l- użu fis- suq: mġieba mhux normali, rabja, ansjetà, konfużjoni, alluċinazzjonijiet, disturbi psikotiċi, attentati ta’ suwiċidju u ħsieb ta ’ suwiċidju
Common: abdominal pain, diarrhoea, dyspepsia, nausea, vomiting Post-marketing experience: pancreatitis
18 Esperjenza wara li l- użu tal- prodott fis- suq: pankreatite
19 Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Keppra overdoses.
Sintomi Wara dożi eċċessivi ta 'Keppra, ġew osservati effetti ta' ħedla, aġitazzjoni, aggressjoni, tnaqqisfil- livell ta 'kuxjenza, livell baxx tar- rifless respiratorju, u koma.
After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis.
X' għandek tagħmel f' każ ta 'doża eċċessiva Wara doża eċċessiva akuta, l- istonku jista' jiġi mbattal permezz ta 'ħasil ta ’ l- istonku jew billi l- pazjent jinġiegħel jirremetti.
The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of α -ethyl-2-oxo-1- pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.
19 Is- sustanza attiva, levetiracetam hija derivattiva ta 'pyrrolidone (S- enantiomer ta ’ α- ethyl- 2- oxo- 1 - pyrrolidine acetamide), u ma jixbahx kimikament lil sustanzi attivi oħrajn li jintużaw kontra l - epilessija.
20 In pediatric patients (4 to 16 years of age), levetiracetam efficacy was established in a double-blind, placebo-controlled study, which included 198 patients and had a treatment duration of 14 weeks.
F’ pazjenti pedjatriċi (4 sa 16 il- sena), l- effiċjenza ta ’ levetiracetam kiem muri f ’ studju double- blind ikkontrollat minn plaċebo li inkluda 198 pazjent b’ trattament li dam 14 il- ġimgħa.
44.6% of the levetiracetam treated patients and 19.6% of the patients on placebo had a 50% or greater reduction from baseline in the partial onset seizure frequency per week.
44. 6% ta ’ pazjenti fuq levetiracetam u 19. 6% ta ’ pazjenti fuq il- plaċebo kellhom tnaqqis ta ’ 50% jew iżjed mill- linja bażi fil- frekwenza fil- ġimgħa ta ’ aċċessjonijiet tat- tip parzjali.
The patients were randomized to carbamazepine CR 400 – 1200 mg/ day or levetiracetam 1000 – 3000 mg/ day, the duration of the treatment was up to 121 weeks depending on the response.
20 carbamazepine CR 400- 1200 mg/ ġurnata jew levetiracetam 1000- 3000 mg/ ġurnata, b’ trattament li dam sa 121 ġimgħa skond kemm kien ir- rispons.
Levetiracetam efficacy was established in a 24-week double-blind, placebo-controlled study, which included adults, adolescents and a limited number of children suffering from idiopathic generalized epilepsy with primary generalized tonic-clonic (PGTC) seizures in different syndromes (juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with Grand Mal seizures on awakening).
L- effikaċja ta ’ levetiracetam kienet stabbilita f’ studju double- blind, ikkontrollat minn plaċebo ta ’ 24 ġimgħa, li inkludiet adulti, addoloxxenti u numru limitat ta ’ tfal b ’ epilessija tat- tip ġeneralizzata idjopatika b’ aċċessjonijiet ġeneralizzati primarji tat- tip tonic- clonic (PGTC) f’ sindromi (epilessija mijoklonika li tibda fiż- żgħożija, epilessija tat- tip absence li tibda fiż- żgħożija, epilessija tat- tip absence fit- tfal, jew epilessija b’ aċċessjonijiet Grand Mal meta jqumu).
21 Levetiracetam is a highly soluble and permeable compound.
Levetiracetam għandu solubilità għolja u huwa permejabbli.
There is no modification of the clearance after repeated administration.
M' hemm ebda differenza fir- rata li biha jitneħħa mill- ġisem wara li jingħata ripetutament.
Absorption
21 Assorbiment
In vitro, levetiracetam and its primary metabolite have been shown not to inhibit the major human liver cytochrome P450 isoforms (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyl transferase (UGT1A1 and UGT1A6) and epoxide hydroxylase activities.
In vitro, kemm levetiracetam u kemm il- prodott ewlieni tal- metabolożmu ma fixklux l- iżoformi taċ - ċitokromju P450 fil- fwied (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 u 1A2), glucuronyl transferase (UGT1A1 u UGT1A6) u l- attivitajiet ta ’ l- epoxide hydroxylase.
The in vitro data and in vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme
Tagħrif in vitro u tagħrif dwar l- interazzjoni in vivo fuq kontraċettivi orali, digoxin u warfarina jindika li mhux mistenni li jkun hemm induzzjoni sinifikanti ta ’ l- enżimi.
Elimination
Eliminazzjoni
The plasma half-life in adults was 7±1 hours and did not vary either with dose, route of administration or repeated administration.
Din ir- rata ma titbiddilx kemm jekk titbiddel id- doża, kemm jekk jitbiddel il- metodu kif jingħata levetiracetam, kif ukoll jekk jingħata ripetutament.
In the elderly, the half-life is increased by about 40% (10 to 11 hours).
22 Fl- anzjani, il- half life ta 'levetiracetam fid- demm tiżdied b’ 40% (10 sa 11 il- siegħa).
23 In subjects with mild and moderate hepatic impairment, there was no relevant modification of the clearance of levetiracetam.
M' hemmx differenzi fir- rata ta 'tneħħija ta' levetiracetam f 'pazjenti b' mard hafif u moderat tal- fwied.
Film-coating Opadry 85F32004:
Il- kisja tar- rita Opadry 85F32004:
Polyvinyl alcohol-part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc Iron oxide yellow (E172)
Polyvinyl alcohol- part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc Iron oxide yellow (E172)
24 Keppra 500 mg film-coated tablets are packaged in aluminium/ PVC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 100, 120 and 200 film-coated tablets.
Keppra 500 mg pilloli miksija b' rita huma ippakkjati f' folji ta ’ l- aluminju/ PVC u mqegħda f 'kaxxi tal - kartun ta' 10, 20, 30, 50, 60, 100, 120 u 200 pillola miksija b' rita.
EU/ 1/ 00/ 146/ 006 EU/ 1/ 00/ 146/ 007 EU/ 1/ 00/ 146/ 008 EU/ 1/ 00/ 146/ 009 EU/ 1/ 00/ 146/ 010 EU/ 1/ 00/ 146/ 011 EU/ 1/ 00/ 146/ 012 EU/ 1/ 00/ 146/ 013
EU/ 1/ 00/ 146/ 006 EU/ 1/ 00/ 146/ 007 EU/ 1/ 00/ 146/ 008 EU/ 1/ 00/ 146/ 009 EU/ 1/ 00/ 146/ 010 EU/ 1/ 00/ 146/ 011
Keppra 750 mg film-coated tablets.
Keppra 750 mg pilloli miksija b' rita.
Each film-coated tablet contains 750 mg levetiracetam Excipient: colouring agent E110.
Sustanza mhux attiva: sustanza li tagħti l- kulur E110
Orange, oblong, scored and debossed with the code “ ucb” and “ 750” on one side.
Oranġjo, tawwalija, maqtuha minn nofs u mnaqqxa bil- kodiċi “ ucb ” u ” 750 ” fuq naħa waħda.
26 Elderly (65 years and older)
Anzjani (65 sena u fuqhom)
Adjustment of the dose is recommended in elderly patients with compromised renal function (see “ Patients with renal impairment ” below).
26 Hu rrikkmandat li f 'pazjenti anzjani li għandhom funzjoni mnaqqsa tal- kliewi, tiġi aġġustata d- doża (ara “ Pazjenti b’ indeboliment tal- kliewi ” hawn taħt).
[140-age (years)] x weight (kg) CLcr (ml/ min) = ----------------------------------------- 72 x serum creatinine (mg/ dl)
[140 - eta` (snin)] x piż (kg) Clcr (ml/ min) =
27 Dosing adjustment for adult patients with impaired renal function
27 Regolar tad- doża f' pazjenti adulti bi ħsara fil- kliewi
28 Therefore patients should be monitored for signs of depression and/ or suicidal ideation and behaviours and appropriate treatment should be considered.
Għalhekk il- pazjenti għandhom jiġu ċċekkjati għal sinjali ta ’ depressjoni u/ jew ħsibijiet u mġieba suwiċidali u għandu jitqies trattament xieraq.
Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/ or suicidal ideation or behaviour emerge.
Il- pazjenti (u dawk li jieħdu ħsieb il- pazjenti) għandhom
Keppra 750 mg film-coated tablets contain E110 colouring agent (see section 4.8).
28 jingħataw il- parir li jfittxu parir mediku jekk jitfaċċaw sinjali ta ’ depressjoni u/ jew ħsibijiet u mġieba suwiċidali.
Therefore, caution is recommended in those patients when performing skilled tasks, e. g. driving vehicles or operating machinery.
Għalhekk, attenzjoni speċjali hi rrikkmandata f' dawn il- pazjenti meta jkunu qed jagħmlu xogħolijiet ta 'ċertu ħila, ez. sewqan ta' vetturi
30 Very common: somnolence Common: amnesia, ataxia, convulsion, dizziness, headache, hyperkinesia, tremor, balance disorder, disturbance in attention, memory impairment.
Komuni ħafna: ħedla Komuni: amneżija, ataksja (movimenti mhux ko- ordinati), aċċessjoni, sturdament, uġigħ ta 'ras, iperkineżja, rogħda, mard tal- bilanċ, disturbi fl- attenzjoni u telf ta ’ memorja.
Common: abdominal pain, diarrhoea, dyspepsia, nausea, vomiting Post-marketing experience: pancreatitis
Komuni: uġigħ fl- addomenu, dijarrea, indiġestjoni, dardir, rimettar Esperjenza wara li l- użu tal- prodott fis- suq: pankreatite
E 110 coloring agent may cause allergic reactions.
Is- sustanza li tagħti l- kulur E110 tista ’ tikkawża reazzjonijiet allerġiċi.
5.1 Pharmacodynamic properties
31 5. 1 Tagħrif farmakodinamiku
The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of α -ethyl-2-oxo-1- pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.
Is- sustanza attiva, levetiracetam hija derivattiva ta 'pyrrolidone (S- enantiomer ta ’ α- ethyl- 2- oxo- 1 - pyrrolidine acetamide), u ma jixbahx kimikament lil sustanzi attivi oħrajn li jintużaw kontra l - epilessija.
32 31.6% and 41.3% for patients on 1000, 2000 or 3000 mg levetiracetam respectively and of 12.6% for patients on placebo.
F’ analisi miġbur, il- perċentaġġ ta ’ pazjenti li laħqu tnaqqis ta ’ 50% jew iżjed mill- linja bażi fil- frekwenza fil- ġimgħa ta ’ aċċessjonijiet tat- tip parzjali b’ doża stabli (12/ 14 ġimgħa), kien ta ’ 27. 7%, 31. 6% u 41. 3% għal pazjenti fuq 1000, 2000, jew 3000 mg ta ’ levetiracetam rispettivament u ta ’ 12. 6% għal pazjenti fuq il- plaċebo.
Efficacy of levetiracetam as monotherapy was established in a double-blind, parallel group, non- inferiority comparison to carbamazepine controlled release (CR) in 576 patients 16 years of age or older with newly or recently diagnosed epilepsy.
32 L- effikaċja ta ’ levetitacetam bħala monoterapija ġiet stabbilita f’ studju li qabblu b’ mod double- blind, parallel group, non- inferiority ma ’ carbamazepine f ’ għamla li jintreħa b ’ mod kontrollat (CR) f’ 576 pazjenti ta ’ 16 il- sena jew iżjed li għadhom kif ġew dijanjostikati b ’ epilessija.
The patients were randomized to carbamazepine CR 400 – 1200 mg/ day or levetiracetam 1000 – 3000 mg/ day, the duration of the treatment was up to 121 weeks depending on the response.
Il- pazjenti kienu maqsuma mingħajr ma ġew magħżula biex jieħdu jew carbamazepine CR 400- 1200 mg/ ġurnata jew levetiracetam 1000- 3000 mg/ ġurnata, b’ trattament li dam sa 121 ġimgħa skond kemm kien ir- rispons.
With continued long-term treatment, 47.4% of
72. 2% ta ’ pazjenti fuq levetiracetam u 45. 2% tal- pazjenti fuq plaċebo kellhom tnaqqis ta ’ 50% jew aktar fil- frekwenza ta ’ aċċessjonijiet PGTC fil- ġimgħa.
33 the patients were free of tonic-clonic seizures for at least 6 months and 31.5% were free of tonic-clonic seizures for at least 1 year.
B’ trattament li jitkompla fit- tul, 47. 4% tal - pazjenti ma kellhomx aċċessjonijiet tat- tip tonic- clonic għal mill- inqas 6 xhur u 31. 5% ma kellhomx aċċessjonijiet tat- tip tonic- clonic għal mill- inqas sena.
A significant correlation between saliva and plasma concentrations has been shown in adults and children (ratio of saliva/ plasma concentrations ranged from 1 to 1.7 for oral tablet formulation and after 4 hours post-dose for oral solution formulation).
33 Intwera korrelazzjoni sinifikanti bejn il- konċentrazzjonijiet fil- bżieq u fil- plażma fl- adulti u fit- tfal (proporzjon ta ’ konċentrazzjonijiet fil- bżieq / plażma kienu f’ medda ta ’ bejn 1 sa 1. 7 b ’ pillola orali u wara 4 siegħat wara d- doża b’ soluzzjoni orali).
34 In human hepatocytes in culture, levetiracetam had little or no effect on CYP1A2, SULT1E1 or UGT1A1.
Levitiracetam kellu ftit jew ebda effett fuq CYP1A2, SULT1E1 jew UGT1A1 f' kolturi ta 'ċelloli tal - fwied umani.
Therefore, the interaction of Keppra with other substances, or vice versa, is unlikely.
Tagħrif in vitro u tagħrif dwar l- interazzjoni in vivo fuq kontraċettivi orali, digoxin u warfarina jindika li mhux mistenni li jkun hemm induzzjoni sinifikanti ta ’ l- enżimi. Għalhekk hija improbabbli li Keppra ma jaqbilx ma 'sustanzi oħra, u viċe versa.
In the elderly, the half-life is increased by about 40% (10 to 11 hours).
Fl- anzjani, il- half life ta 'levetiracetam fid- demm tiżdied b’ 40% (10 sa 11 il- siegħa).
35 Hepatic impairment
Indeboliment tal- fwied
In reproductive toxicity studies in the rat, levetiracetam induced developmental toxicity (increase in skeletal variations/ minor anomalies, retarded growth, increased pup mortality) at exposure levels similar to or greater than the human exposure.
35 Fi studji ta 'tossiċità riproduttiva fil- far, kien hemm tossiċità ta ’ l- iżvilupp bl- użu ta' levetiracetam (żieda fil- varjazzjonijiet skeletali / anomaliji minuri, tkabbir iżjed bil- mod, u żieda fir- rata tal- mewt tal - wild) wara espożizzjonijiet simili jew aktar għolja minn tal- bniedem.
Magnesium stearate
Sodium croscarmellose Macrogol 6000 Colloidal anhydrous silica Magnesium stearate
Film-coating Opadry 85F23452:
Il- kisja tar- rita Opadry 85F23452:
Polyvinyl alcohol-part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc Sunset yellow FCF aluminium lake (E110) Iron oxide red (E172)
Polyvinyl alcohol- part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc Sunset yellow FCF aluminium lake (E110) Iron oxide red (E172)
36 No special precautions for storage.
L- ebda ħtiġijiet speċjali għal ħażna.
Keppra 750 mg film-coated tablets are packaged in aluminium/ PVC blisters placed into cardboard boxes containing 20, 30, 50, 60, 80, 100 and 200 film-coated tablets.
Keppra 750 mg pilloli miksija b' rita huma ippakkjati f' folji ta ’ l- aluminju/ PVC u mqegħda f 'kaxxi tal - kartun ta' 20, 30, 50, 60, 80, 100 u 200 pillola miksija b' rita.
Keppra 1000 mg film-coated tablets.
Keppra 1000 mg pilloli miksija b' rita.
Each film-coated tablet contains 1,000 mg levetiracetam.
Kull pillola miksija b' rita fiha 1, 000 mg levetiracetam.
White, oblong, scored and debossed with the code “ ucb” and “ 1000” on one side.
Bajda, tawwalija, maqtuha minn nofs u mnaqqxa bil- kodiċi “ ucb ” u ” 1000 ” fuq naħa waħda.
38 Adjustment of the dose is recommended in elderly patients with compromised renal function (see “ Patients with renal impairment ” below).
38 (ara “ Pazjenti b’ indeboliment tal- kliewi ” hawn taħt).
20 kg 25 kg From 50 kg (2) (1)
15 kg (1) 20 kg (1) 25 kg Minn 50 kg (2) (1)
200 mg twice daily 250 mg twice daily 500 mg twice daily
150 mg darbtejn kuljum 200 mg darbtejn kuljum 250 mg darbtejn kuljum 500 mg darbtejn kuljum
600 mg twice daily 750 mg twice daily 1500 mg twice daily
450 mg darbtejn kuljum 600 mg darbtejn kuljum 750 mg darbtejn kuljum 1500 mg darbtejn kuljum
[140-age( years)] x weight (kg) CLcr (ml/ min) = ----------------------------------------- 72 x serum creatinine (mg/ dl)
[140 - eta` (snin)] x piż (kg) Clcr (ml/ min) =
39 Dosing adjustment for adult patients with impaired renal function
39 Regolar tad- doża f' pazjenti adulti bi ħsara fil- kliewi
40 Therefore patients should be monitored for signs of depression and/ or suicidal ideation and behaviours and appropriate treatment should be considered.
Għalhekk il- pazjenti għandhom jiġu ċċekkjati għal sinjali ta ’ depressjoni u/ jew ħsibijiet u mġieba suwiċidali u għandu jitqies trattament xieraq.
4.5 Interaction with other medicinal products and other forms of interaction
40 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
41 No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq jew tħaddem magni.
4.8 Undesirable effects
41 4. 8 Effetti mhux mixtieqa
42 Common: amnesia, ataxia, convulsion, dizziness, headache, hyperkinesia, tremor, balance disorder, disturbance in attention, memory impairment.
Komuni ħafna: ħedla Komuni: amneżija, ataksja (movimenti mhux ko- ordinati), aċċessjoni, sturdament, uġigħ ta 'ras, iperkineżja, rogħda, mard tal- bilanċ, disturbi fl- attenzjoni u telf ta ’ memorja.
Common: abdominal pain, diarrhoea, dyspepsia, nausea, vomiting Post-marketing experience: pancreatitis
42 Esperjenza wara li l- użu tal- prodott fis- suq: pankreatite
43 Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Keppra overdoses.
Sintomi Wara dożi eċċessivi ta 'Keppra, ġew osservati effetti ta' ħedla, aġitazzjoni, aggressjoni, tnaqqisfil- livell ta 'kuxjenza, livell baxx tar- rifless respiratorju, u koma.
The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of α -ethyl-2-oxo-1- pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.
43 Is- sustanza attiva, levetiracetam hija derivattiva ta 'pyrrolidone (S- enantiomer ta ’ α- ethyl- 2- oxo- 1 - pyrrolidine acetamide), u ma jixbahx kimikament lil sustanzi attivi oħrajn li jintużaw kontra l - epilessija.
44 In pediatric patients (4 to 16 years of age), levetiracetam efficacy was established in a double-blind, placebo-controlled study, which included 198 patients and had a treatment duration of 14 weeks.
F’ pazjenti pedjatriċi (4 sa 16 il- sena), l- effiċjenza ta ’ levetiracetam kiem muri f ’ studju double- blind ikkontrollat minn plaċebo li inkluda 198 pazjent b’ trattament li dam 14 il- ġimgħa.
The patients were randomized to carbamazepine CR 400 – 1200 mg/ day or levetiracetam 1000 – 3000 mg/ day, the duration of the treatment was up to 121 weeks depending on the response.
44 carbamazepine CR 400- 1200 mg/ ġurnata jew levetiracetam 1000- 3000 mg/ ġurnata, b’ trattament li dam sa 121 ġimgħa skond kemm kien ir- rispons.
45 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
Absorption
45 Assorbiment
The in vitro data and in vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme 46 induction is expected in vivo.
Tagħrif in vitro u tagħrif dwar l- interazzjoni in vivo fuq kontraċettivi orali, digoxin u warfarina jindika li mhux mistenni li jkun hemm induzzjoni sinifikanti ta ’ l- enżimi.
Elderly
46 Anzjani
Linear and dose proportional increases were observed for peak plasma concentration and area under the curve.
Żiediet linejari u proporzjonali għad- doża kienu osservati bil - konċentrazzjonijiet massimi fil- plażma u l- erja taħt il- kurva.
47 In subjects with mild and moderate hepatic impairment, there was no relevant modification of the clearance of levetiracetam.
M' hemmx differenzi fir- rata ta 'tneħħija ta' levetiracetam f 'pazjenti b' mard hafif u moderat tal- fwied.
In the rabbit foetal effects (embryonic death, increased skeletal anomalies, and increased malformations) were observed in the presence of maternal toxicity.
Fil- fenek, effetti fuq il- fetu (mewt ta ’ l- embriju, żieda fl- anomaliji skeletali u żieda fil- malformazzjonijiet) ġew osservati meta kien
The systemic exposure at the observed no effect level in the rabbit was about 4 to 5 times the human exposure.
47 hemm tossiċità fl- omm.
Neonatal and juvenile animal studies in rats and dogs demonstrated that there were no adverse effects seen in any of the standard developmental or maturation endpoints at doses up to 1800 mg/ kg/ day corresponding to 30 times the maximum recommended human dose.
Ebda effett ma kien osservat fil- fenek meta l- livell fid- demm kien minn 4 sa 5 darbiet ta 'dak fil- bniedem.
Film-coating Opadry 85F18422:
Il- kisja tar- rita Opadry 85F18422:
Polyvinyl alcohol-part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc
Polyvinyl alcohol- part. hydrolyzed Titanium dioxide (E171) Macrogol 3350 Talc
48 Keppra 1000 mg film-coated tablets are packaged in aluminium/ PVC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 100 and 200 film-coated tablets.
Keppra 1000 mg pilloli miksija b' rita huma ippakkjati f' folji ta ’ l- aluminju/ PVC u mqegħda f 'kaxxi tal- kartun ta' 10, 20, 30, 50, 60, 100 u 200 pillola miksija b' rita.
EU/ 1/ 00/ 146/ 020 EU/ 1/ 00/ 146/ 021 EU/ 1/ 00/ 146/ 022 EU/ 1/ 00/ 146/ 023 EU/ 1/ 00/ 146/ 024 EU/ 1/ 00/ 146/ 025 EU/ 1/ 00/ 146/ 026
EU/ 1/ 00/ 146/ 020 EU/ 1/ 00/ 146/ 021 EU/ 1/ 00/ 146/ 022 EU/ 1/ 00/ 146/ 023
Keppra 100 mg/ ml oral solution.
Keppra 100 mg/ ml soluzzjoni orali.
Each ml contains 100 mg levetiracetam Excipients: methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216) and 300 mg maltitol.
Kull ml fiha 100 mg levetiracetam.
For a full list of excipients, see section 6.1.
Sustanzi mhux attivi: methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216) u 300 mg maltitol.
Clear liquid.
Likwidu ċar.
Keppra is indicated as adjunctive therapy • in the treatment of partial onset seizures with or without secondary generalisation in adults and children from 4 years of age with epilepsy. • in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy. • in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.
Keppra huwa indikat biex ikun użat bħala parti mit- terapija • fit- trattament ta 'aċċessjonijiet tat- tip parzjali kemm meta jkun hemm, kif ukoll meta ma jkunx hemm ġeneralizzazzjoni sekondarja f ’ adulti u tfal minn 4 snin b’ epilessija. • fit- trattament ta ’ aċċessjonijiet tat- tip mijokloniċi f’ adulti u addoloxxenti minn 12 snin b’ epilessija tat- tip Mijoklonika li tibda fiż- żgħożija • Fit- trattament ta ’ aċċessjonijiet primarji u ġeneralizzati tat- tip tonic- clonic f’ adulti u addoloxxenti minn 12 il- sena b’ Epilessija Ġeneralizzata Idjopatika.
The oral solution may be diluted in a glass of water and may be taken with or without food.
Is- soluzzjoni likwida tista ’ titħallat ma ’ tazza ilma u tista ’ tittieħed kemm ma 'l- ikel, kif ukoll fuq stonku vojt.
A graduated oral syringe and instructions for use in the package leaflet are provided with Keppra.
Ma 'Keppra issib siringa orali mmarkata bil- kejl flimkien ma' istruzzjonijiet ta 'kif għandha tintuża fil- fuljett ta' tagħrif.
50 Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily.
Id- doża ta 'kuljum tista' tiġi miżjuda jew mnaqqsa għal massimu ta '1, 500 mg darbtejn kuljum, skond ir- respons kliniku u skond kemm il- mediċina tkun indrat mill- pazjent.
Elderly (65 years and older)
50 Anzjani (65 sena u fuqhom)
Adjustment of the dose is recommended in elderly patients with compromised renal function (see “ Patients with renal impairment ” below).
Hu rrikkmandat li f 'pazjenti anzjani li għandhom funzjoni mnaqqsa tal- kliewi, tiġi aġġustata d- doża (ara “ Pazjenti b’ indeboliment tal- kliewi ” hawn taħt).
Starting dose:
Doża Massima:
10 mg/ kg twice daily
Piż Doża tal- bidu:
30 mg/ kg twice daily
30 mg/ kg darbtejn kuljum 10 mg/ kg darbtejn kuljum
The graduated oral syringe contains up to 1,000 mg levetiracetam (corresponding to 10 ml) with a graduation every 25 mg (corresponding to 0.25 ml).
Is- siringa orali mmarkata bil- kejl tesa ’ sa 1, 000 mg levetiracetam (jikkorrespondi għal 10ml) b ’ marka kull 25 mg (jikkorrispondi għal 0. 25ml).
51 Dosing adjustment for adult patients with impaired renal function
51 Regolar tad- doża f' pazjenti adulti bi ħsara fil- kliewi
52 Therefore patients should be monitored for signs of depression and/ or suicidal ideation and behaviours and appropriate treatment should be considered.
Għalhekk il- pazjenti għandhom jiġu ċċekkjati għal sinjali ta ’ depressjoni u/ jew ħsibijiet u mġieba suwiċidali u għandu jitqies trattament xieraq.
Keppra 100 mg/ ml oral solution includes methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216) which may cause allergic reactions (possibly delayed).
52 Keppra soluzzjoni orali tinkludi methyl parahydroxybenzoate (E218) u propyl parahydroxybenzoate (E216) li jistgħu jikkawżaw reazzjonijiet allerġiċi (li jistgħu jieħdu iż - żmien biex jidhru).
It also includes maltitol; patients with rare hereditary problems of fructose intolerance should not take this medicine.
Jinkludi wkoll maltitol; pazjenti bi problemi ereditarji rari ta ’ intoleranza għal fructose m’ għandhomx jieħdu din il- mediċina.
Keppra should not be used during pregnancy unless clearly necessary.
Keppra m' għandux jintuża waqt it- tqala sakemm mhux veru neċessarji.
Due to possible different individual sensitivity, some patients might experience somnolence or other central nervous system related symptoms, especially at the beginning of treatment or following a dose increase.
Speċjalment fil- bidu tat - trattament jew wara żieda fid- doża, xi pazjenti li possibilment ikunu iżjed sensittivi, jistgħu jitħeddlu
54 Very common: asthenia/ fatigue.
Komuni ħafna: astenja/ għajja.
Common: agitation, depression, emotional lability/ mood swings, hostility/ aggression, insomnia, nervousness/ irritability, personality disorders, thinking abnormal Post-marketing experience: abnormal behaviour, anger, anxiety, confusion, hallucination, psychotic disorder, suicide, suicide attempt and suicidal ideation
Komuni: aġitazzjoni, depressjoni, disturbi emozzjonali, tibdil fil- burdata, ostilità / aggressjoni, nuqqas ta 'rqad, nervożita`/ irritabilita`, disturbi fil- personalita`, ħsieb mhux normali
- Respiratory, thoracic and mediastinal disorders
Mard respiratorju, toraċiku u medjastinali
Common: thrombocytopenia Post-marketing experience: leukopenia, neutropenia, pancytopenia (with bone marrow suppression identified in some of the cases).
Esperjenza wara l- użu fis- suq: lukopenja, nutropenja, panċitopenja (b ’ soppressjoni tal- mudullun identifikat f’ xi każi)
55 Symptoms Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with Keppra overdoses.
Sintomi Wara dożi eċċessivi ta 'Keppra, ġew osservati effetti ta' ħedla, aġitazzjoni, aggressjoni, tnaqqisfil- livell ta 'kuxjenza, livell baxx tar- rifless respiratorju, u koma.
Management of overdose After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis.
X' għandek tagħmel f' każ ta 'doża eċċessiva Wara doża eċċessiva akuta, l- istonku jista' jiġi mbattal permezz ta 'ħasil ta ’ l- istonku jew billi l- pazjent jinġiegħel jirremetti.
5.1 Pharmacodynamic properties
55 5. 1 Tagħrif farmakodinamiku
N03AX14 The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of α -ethyl-2-oxo-1- pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.
Is- sustanza attiva, levetiracetam hija derivattiva ta 'pyrrolidone (S- enantiomer ta ’ α- ethyl- 2- oxo- 1 - pyrrolidine acetamide), u ma jixbahx kimikament lil sustanzi attivi oħrajn li jintużaw kontra l - epilessija.
Pharmacodynamic effects Levetiracetam induces seizure protection in a broad range of animal models of partial and primary generalised seizures without having a pro-convulsant effect.
Dan jsir mingħajr ma jkollu l- effett li jikkawża aċċessjonijiet.
56 In pediatric patients (4 to 16 years of age), levetiracetam efficacy was established in a double-blind, placebo-controlled study, which included 198 patients and had a treatment duration of 14 weeks.
F’ pazjenti pedjatriċi (4 sa 16 il- sena), l- effiċjenza ta ’ levetiracetam kiem muri f ’ studju double- blind ikkontrollat minn plaċebo li inkluda 198 pazjent b’ trattament li dam 14 il- ġimgħa.
Efficacy of levetiracetam as monotherapy was established in a double-blind, parallel group, non- inferiority comparison to carbamazepine controlled release (CR) in 576 patients 16 years of age or older with newly or recently diagnosed epilepsy.
56 L- effikaċja ta ’ levetitacetam bħala monoterapija ġiet stabbilita f’ studju li qabblu b’ mod double- blind, parallel group, non- inferiority ma ’ carbamazepine f ’ għamla li jintreħa b ’ mod kontrollat (CR) f’ 576 pazjenti ta ’ 16 il- sena jew iżjed li għadhom kif ġew dijanjostikati b ’ epilessija.
The patients were randomized to carbamazepine CR 400 – 1200 mg/ day or levetiracetam 1000 – 3000 mg/ day, the duration of the treatment was up to 121 weeks depending on the response.
Il- pazjenti kienu maqsuma mingħajr ma ġew magħżula biex jieħdu jew carbamazepine CR 400 - 1200 mg/ ġurnata jew levetiracetam 1000 - 3000 mg/ ġurnata, b’ trattament li dam sa 121 ġimgħa skond kemm kien ir- rispons.
57 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
A significant correlation between saliva and plasma concentrations has been shown in adults and children (ratio of saliva/ plasma concentrations ranged from 1 to 1.7 for oral tablet formulation and after 4 hours post-dose for oral solution formulation).
57 Intwera korrelazzjoni sinifikanti bejn il- konċentrazzjonijiet fil- bżieq u fil- plażma fl- adulti u fit- tfal (proporzjon ta ’ konċentrazzjonijiet fil- bżieq / plażma kienu f’ medda ta ’ bejn 1 sa 1. 7 b ’ pillola orali u wara 4 siegħat wara d- doża b’ soluzzjoni orali).
In human hepatocytes in culture, levetiracetam had little or no effect on CYP1A2, SULT1E1 or UGT1A1.
Levitiracetam kellu ftit jew ebda effett fuq CYP1A2, SULT1E1 jew UGT1A1f' kolturi ta 'ċelloli tal- fwied umani..
The in vitro data and in vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme 58 induction is expected in vivo.
Tagħrif in vitro u tagħrif dwar l- interazzjoni in vivo fuq kontraċettivi orali, digoxin u warfarina jindika li mhux mistenni li jkun hemm induzzjoni sinifikanti ta ’ l- enżimi.
59 In subjects with mild and moderate hepatic impairment, there was no relevant modification of the clearance of levetiracetam.
M' hemmx differenzi fir- rata ta 'tneħħija ta' levetiracetam f 'pazjenti b' mard hafif u moderat tal- fwied.
In reproductive toxicity studies in the rat, levetiracetam induced developmental toxicity (increase in skeletal variations/ minor anomalies, retarded growth, increased pup mortality) at exposure levels similar to or greater than the human exposure.
59 Fi studji ta 'tossiċità riproduttiva fil- far, kien hemm tossiċità ta ’ l- iżvilupp bl- użu ta' levetiracetam (żieda fil- varjazzjonijiet skeletali / anomaliji minuri, tkabbir iżjed bil- mod, u żieda fir- rata tal- mewt tal - wild) wara espożizzjonijiet simili jew aktar għolja minn tal- bniedem.
Sodium citrate Citric acid monohydrate Methyl parahydroxybenzoate (E218) Propyl parahydroxybenzoate (E216) Ammonium glycyrrhizate Glycerol (E422) Maltitol (E965) Acesulfame potassium (E950) Grape flavour Purified water
Sodium citrate Citric acid monohydrate Methyl parahydroxybenzoate (E218) Propyl parahydroxybenzoate (E216) Ammonium glycyrrhizate Glycerol (E422) Maltitol (E965) Acesulfame potassium (E950) Essenza ta ’ l- għeneb Ilma purifikat,
Finished product:
Prodott lest:
2 years.
2 snin.
2 months
Wara l- ewwel darba li jinfetaħ: xagħrejn
60 300 ml amber glass bottle (type III) with a white child resistant closure (polypropylene) in a cardboard box also containing a graduated oral syringe (polyethylene, polystyrene) and a patient information leaflet.
Dan issibu ġo kaxxa tal- kartun li fiha wkoll siringa orali mmarkata bil- kejl (polyethylene, polystyrene) u fuljett ta 'tagħrif għall- pazjent.
Keppra 100 mg/ ml concentrate for solution for infusion.
Keppra 100 mg/ ml konċentrat għal soluzzjoni għall- infużjoni.
Each ml contains 100 mg of levetiracetam.
Kull ml fiha 100 mg ta ’ levetiracetam.
The 5 ml vial contains 500 mg of levetiracetam.
Il- vjala ta ’ 5 ml fiha 500 mg ta ’ levetiracetam.
Concentrate for solution for infusion.
Konċentrat għal soluzzjoni għall- infużjoni.
Keppra concentrate is a clear, colorless, sterile solution.
Il- konċentrat Keppra huwa soluzzjoni ċara, bla kulur u sterili.