qanastek/EMEA-V3 huggingface dataset:
There have been reports of central nervous system events including dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine following the introduction of lamotrigine.
Kien hemm xi rapporti ta ’ reazzjonijiet fis- sistema nervuża ċentrali fosthom sturdamenti, atassija, diplopija, vista mċajpra u dardir f’ pazjenti li ħadu carbamazepine wara li bdew lamotrigine.
These events usually resolve when the dose of carbamazepine is reduced.
Dawn ir- reazzjonijiet ġeneralment jgħaddu meta titnaqqas id- doża ta ’ carbamazepine.
A similar effect was seen during a study of lamotrigine and oxcarbazepine in healthy adult volunteers, but dose reduction was not investigated.
Effett bħal dan deher ukoll fi studju dwar lamotrigone u oxcarbazepine fuq voluntieri adulti f’ saħħithom, biss ma sarux studji dwar tnaqqis tad- doża.
There are reports in the literature of decreased lamotrigine levels when lamotrigine was given in combination with oxcarbazepine.
64 Kien hemm xi rapporti fil- letteratura ta ’ livelli anqas ta’ lamotrigine meta lamotrigine intuża flimkien ma ’ oxycarbazepine.
60 doses of 200 mg lamotrigine and 1200 mg oxcarbazepine, oxcarbazepine did not alter the metabolism of lamotrigine and lamotrigine did not alter the metabolism of oxcarbazepine.
Madankollu, fi studju prospettiv fuq voluntieri adulti f’ saħħithom b’ dożi ta ’ 200 mg lamotrigine u 1200 mg oxcarbazepine, oxcarbazepine ma bidilx il- metaboliżmu ta ’ lamotrigine u lamotrigine ma bidlix il- metaboliżmu ta ’ oxcarbazepine.
Therefore in patients receiving concomitant therapy with oxcarbazepine, the treatment regimen for lamotrigine adjunctive therapy without valproate and without inducers of lamotrigine glucuronidation should be used (see section 4.2).
Għalhekk f’ pazjenti li jirċievu kura flimkien ma ’ oxycarbazepine, għandha tintuża is- sistema ta ’ kura għal terapija aġġuntiva b’ lamotrigine, mingħajr valproate u mingħajr inducers ta ’ glukorinidzzjoni ta ’ lamotrigine (ara s- sezzjoni 4. 2).
In a study of healthy volunteers, coadministration of felbamate (1200 mg twice daily) with lamotrigine (100 mg twice daily for 10 days) appeared to have no clinically relevant effects on the pharmacokinetics of lamotrigine.
Fi studju fuq voluntieri f’ saħħithom, it- teħid flimkien ta ’ felbamate (1200 mg darbtejn kuljum) ma ’ lamotrigine (100 mg darbtejn kuljum għal 10 ġranet) ma deher li kellu ebda effetti rilevanti kliniċi fuq il - farmakokinetiċi ta ’ lamotrigine.
Based on a retrospective analysis of plasma levels in patients who received lamotrigine both with and without gabapentin, gabapentin does not appear to change the apparent clearance of lamotrigine.
Fuq il- bażi ta ’ analiżi retrospettiva ta ’ livelli ta ’ plasma f’ pazjenti li kienu ħadu lamotrigine bi jew mingħajr gabapentin, gabapentin ma deherx li biddel it- tneħħija fid- dehra ta ’ lamotrigine.
Potential interactions between levetiracetam and lamotrigine were assessed by evaluating serum concentrations of both agents during placebo-controlled clinical trials.
Il- possibilta ’ li levetiracetam u lamotrigine ma jkunux jaqblu ma ’ xulxin ġiet assessjata bl- evalwazzjoni ta ’ konċentrazzjonijiet ta ’ serum taż- żewġ aġenti waqt provi kliniċi kontrollati bi plaċebo.
These data indicate that lamotrigine does not influence the pharmacokinetics of levetiracetam and that levetiracetam does not influence the pharmacokinetics of lamotrigine.
Dan it- tagħrif jindika li lamotrigine ma jinfluwenzax il- farmakokinetiċi ta ’ levetiracetam u li levetiracetam ma jinfluwenzax il- farmakokinetiċi ta ’ lamotrigine.
Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin (200 mg, 3 times daily) administration.
Konċentrazzjonijiet steady- state trough ta ’ lamotrigine fil- plażma ma ġewx affettwati meta ttieħed pregabalin (200 mg, 3 darbiet kuljum) fl- istess ħin.
There are no pharmacokinetic interactions between lamotrigine and pregabalin.
Ma hemmx problemi ta ’ interazzjoni fil- farmakokinetiċi ta ’ bejn lamotrigine u pregabalin.
Topiramate resulted in no change in plasma concentrations of lamotrigine.
Topiramate ma rriżulta f’ ebda bidla fil- konċentrazzjonijiet ta ’ plasma ta ’ lamotrigine.
Administration of lamotrigine resulted in a 15% increase in topiramate concentrations.
L- għoti ta ’ lamotrigine irriżulta f’ żjieda ta ’ 15% fil- konċentrazzjonijiet ta ’ topiramate.
In a study of patients with epilepsy, coadministration of zonisamide (200 to 400 mg/ day) with lamotrigine (150 to 500 mg/ day) for 35 days had no significant effect on the pharmacokinetics of lamotrigine.
Fi studju fuq pazjenti b’ epilessija, l- għoti flimkien ta’ zonisamide (200 sa 400 mg mg/ kuljum) ma ’ lamotrigine (160 sa 500 mg/ kuljum) għal 35 jum ma kellu ebda effett sinifikanti fuq il- farmakokinetiċi ta ’ lamotrigine.
Although changes in the plasma concentrations of other AEDs have been reported, controlled studies have shown no evidence that lamotrigine affects the plasma concentrations of concomitant AEDs.
Għalkemm bdil fil- konċentrazzjonijiet ta ’ plasma ta ’ AEDs oħra ġie rappurtat, studji kontrollati ma wrew ebda evidenza li lamotrigine jaffettwa l- konċentrazzjonijiet ta ’ plasma ta ’ AEDs meta jittieħdu flimkien.
Evidence from in vitro studies indicates that lamotrigine does not displace other AEDs from protein binding sites.
Evidenza minn studji in vitro tindika li lamotrigine ma jieħux post AEDs oħra f’ siti li jwaħħlu l- proteini.
Interactions involving other psychoactive agents
Interazzjonijiet li jinvolvu aġenti oħra psikoattivi
The pharmacokinetics of lithium after 2 g of anhydrous lithium gluconate given twice daily for six days to 20 healthy subjects were not altered by co-administration of 100 mg/ day lamotrigine.
Il- farmakokinetiċi ta ’ litju wara 2g ta ’ anhydrous lithium gluconate mogħti darbtejn kuljum għal sitt ijiem lil 20 individwi f’ saħħithom ma nbidlux bl- għoti flimkien ta ’ 100 mg/ kuljum lamotrigine.
Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of lamotrigine in 12 subjects and had only a slight increase in the AUC of lamotrigine glucuronide.
L- għoti ta ’ ħafna dożi ta ’ bupropion ma ’ kellu ebda effett sinifikanti ta ’ statistika fuq il- farmakokinetiċi ta ’ doża waħda ta ’ lamotrigine fi 12- il persuna u wera biss żjieda żgħira fl- AUC tal- glukuronid ta ’ lamotrigine.
In a study in healthy adult volunteers, 15 mg olanzapine reduced the AUC and Cmax of lamotrigine by an average of 24% and 20%, respectively.
Fi studju fuq numru ta ’ voluntieri f’ saħħithom, 15 mg olanzapine naqqsu l- AUC u Cmax ta ’ lamotrigine b’ medja ta ’ 24% u 20% rispettivament.
An effect of this magnitude is not generally expected to be clinically relevant.
Effett ta ’ dan il- kobor mhuwiex ġeneralment mistenni li jkun ta ’ rilevanza klinika.
Lamotrigine at 200 mg did not affect the pharmacokinetics of olanzapine.
Lamotrigine b’ doża ta ’ 200 mg ma kellu ebda effett fuq il- farmakokinetiċi ta ’ olanzapine.
Multiple oral doses of lamotrigine 400 mg daily had no clinically significant effect on the single dose pharmacokinetics of 2 mg risperidone in 14 healthy adult volunteers.
Numru ta ’ dożi orali ta ’ 400 mg lamotrigine kuljum ma kellu ebda effett sinifikanti kliniku fuq il - farmakokinetiċi ta ’ doża waħda ta ’ 2 mg risperidone f’ 14 voluntieri f’ saħħithom.
Following the co-administration of risperidone 2 mg with lamotrigine, 12 out of the 14 volunteers reported somnolence compared to 1 out of 20 when risperidone was given alone, and none when lamotrigine was administered alone.
Wara li ħadu 2 mg risperidone flimkien ma ’ lamotrigine, 12 mill- 14 voluntieri rrappurtaw ħedla ta ’ rqad meta mqabbla ma ’ 1 minn 20 li ngħataw risperidone waħdu, u ħadd minnhom meta lamotrigine ingħata waħdu.
In vitro experiments indicated that the formation of lamotrigine's primary metabolite, the 2-N-glucuronide, was minimally inhibited by co-incubation with amitriptyline, bupropion, clonazepam, haloperidol or lorazepam.
Esperimenti in vitro indikaw li l- formazzjoni tal - metabolit primarju ta ’ lamotrigine, il- glukuronid 2- N, ġie kemm kemm inibit b’ ko- inkubazzjoni ma ’ amitriptyline, bupropion, clonazepam, haloperidol jew lorazepam.
These experiments also suggested that metabolism of lamotrigine was unlikely to be inhibited by clozapine, fluoxetine, phenelzine, risperidone, sertraline or
Dawn l- esperimenti indikaw ukoll li l- metaboliżmu ta ’ lamotrigine mhux probabbli li jkun inibit
61 trazodone.
65 bi clozapine, fluoxetene, phenelzine, risperidone, sertraline jew trazodone.
In addition, a study of bufuralol metabolism using human liver microsome preparations suggested that lamotrigine would not reduce the clearance of medicinal products metabolised predominantly by CYP2D6.
Barra dan, studju dwar il - metaboliżmu ta ’ bufuralol bl- użu ta ’ preparamenti ta ’ mikrosomi tal- fwied uman indikaw li lamotrigine ma jnaqqasx mit- tneħħija ta ’ prodotti mediċinali metabolizzati prinċipalment b’ CYP2D6.
Interactions involving hormonal contraceptives
Interazzjonijiet li jinvolvu kontraċettivi ormonali
Effect of hormonal contraceptives on lamotrigine pharmacokinetics In a study of 16 female volunteers, dosing with 30 µg ethinyloestradiol/ 150 µg levonorgestrel in a combined oral contraceptive pill caused an approximately two-fold increase in lamotrigine oral clearance, resulting in an average 52% and 39% reduction in lamotrigine AUC and Cmax, respectively.
Effett ta ’ kontraċettivi ormonali fuq il- farmakokinetiċi ta ’ lamotrigine Fi studju fuq 16 voluntieri nisa, dożaġġ ta ’ 30 µg ethinyloestradiol/ 150 µg levonorgestrel f’ pillola kontraċettiva kombinata li tittieħed mill- ħalq ikkawżat żjieda ta ’ aktar minn darbtejn f’ dik li hi tneħħija orali ta ’ lamotrigine, b’ riżultat ta ’ tnaqqis medju ta ’ 52% u 39% fl- AUC u Cmax ta ’ lamotrigine, rispettivament.
Serum lamotrigine concentrations increased during the course of the week of inactive treatment (including the "pill-free" week), with pre-dose concentrations at the end of the week of inactive treatment being, on average, approximately two-fold higher than during co-therapy (see section 4.4).
Il- konċentrazzjonijiet ta ’ lamotrigine fis- serum żdiedu matul il- ġimgħa ta ’ trattament mhux attiv (inkluża l - ġimgħa “ bla pilloli ”), bil- konċentrazzjonijiet ta ’ qabel it- teħid tad- dożi fl- aħħar tal- ġimgħa ta ’ trattament mhux attiv jibqgħu, bħala medja, darbtejn aktar minn dawk ta ’ waqt il- ko- terapija (ara sezzjoni 4. 4).
No adjustments to the recommended dose escalation guidelines for lamotrigine should be necessary solely based on the use of hormonal contraceptives, but the maintenance dose of lamotrigine will need to be increased or decreased in most cases when starting or stopping hormonal contraceptives (see section 4.2).
Ebda aġġustamenti m’ għandhom ikunu neċessarji għal- linji gwida rakkomandati dwar iż- żjieda tad- dożi ta ’ lamotrigine li jkunu bażati biss fuq l- użu ta ’ kontraċettivi ormonali, iżda d- doża ta ’ stabbilizzazzjoni ta ’ lamotrigine ikun hemm bżonn li tiżdied jew titnaqqas fil- parti l- kbira ta ’ każijiet meta jinbdew jew jitwaqqfu l- kontraċettivi ormonali (ara sezzjoni 4. 2).
Effect of lamotrigine on hormonal contraceptive pharmacokinetics In a study of 16 female volunteers, a steady state dose of 300 mg lamotrigine had no effect on the pharmacokinetics of the ethinyloestradiol component of a combined oral contraceptive pill.
Effett ta ’ lamotrigine fuq il- farmakokinetiċi ta ’ kontraċettivi ormonali Fi studju fuq 16 voluntieri nisa, doża steady- state ta ’ 300 mg lamotrigine ma kella ebda effett fuq il - farmakokinetiċi tal- komponent ethinyloestradiol ta ’ pillola kontraċettiva orali kombinata.
A modest increase in oral clearance of the levonorgestrel component was observed, resulting in an average 19% and 12% reduction in levonorgestrel AUC and Cmax, respectively.
Giet osservata żjieda żgħira fit- tneħħija orali tal- komponent levonorgestrel, li rriżultat fi tnaqqis medju ta ’ 19% u 12% mill- AUC u Cmax ta ’ levonorgestrel, rispettivament.
Measurement of serum FSH, LH and oestradiol during the study indicated some loss of suppression of ovarian hormonal activity in some women, although measurement of serum progesterone indicated that there was no hormonal evidence of ovulation in any of the 16 subjects.
Il- kejl ta ’ FSH, LH u oestradiol fis- serum waqt l - istudju wera xi tnaqqis ta ’ soppressjoni fl- attivita ’ ormonali ta ’ l- ovarju f’ xi wħud min- nisa, għalkemm il - kejl ta ’ progesterone tas- serum indika li ma kien hemm ebda evidenza ormonali ta ’ ovulazzjoni f’ xi waħda mis- 16- il mara.
The impact of the modest increase in levonorgestrel clearance, and the changes in serum FSH and LH, on ovarian ovulatory activity is unknown (see section 4.4).
L- impatt taż- żjieda żgħira fit- tneħħija ta ’ levonorgestrel, u l- bidliet fl- FSH u LH tas- serum fuq l- attivita ’ ovulatorja ta ’ l- ovarju mhux magħruf (ara sezzjoni 4. 4).
The effects of doses of lamotrigine other than 300 mg/ day have not been studied and studies with other female hormonal preparations have not been conducted.
L- effetti ta ’ dożi ta ’ lamotrigine għajr it- 300 mg/ kuljum ma ġewx studjati u lanqas ma saru studji bi preparazzjonijiet ormonali oħra tan- nisa.
Interactions involving other medicinal products
Interazzjonijiet li jinvolvu prodotti mediċinali oħra
In a study in 10 male volunteers, rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation.
Fi studju fuq 10 voluntieri rġiel, rifampicin żied it- tneħħija ta ’ lamotrigine u naqqas il- half- life ta ’ lamotrigine minħabba l- induzzjoni ta ’ l- enzimi tal- fwied risponsabbli għall- glukuronodazzjoni.
In patients receiving concomitant therapy with rifampicin, the appropriate treatment regimen should be used (see section 4.2).
F’ pazjenti li jkunu fuq terapija konkomitanti b’ rifampicin, għandu jintuża l- programm xieraq ta ’ trattament (ara sezzjoni 4. 2).
In a study in healthy volunteers, lopinavir/ ritonavir approximately halved the plasma concentrations of lamotrigine, probably by induction of glucuronidation.
Fi studju fuq voluntieri f’ saħħithom, lopinavir/ ritonavir naqqsu b’ madwar in- nofs il- konċentrazzjonijiet ta ’ plasma ta ’ lamotrigine, probabbilment bl- induzzjoni ta ’ glukuronidazzjoni.
In patients receiving concomitant therapy with lopinavir/ ritonavir, the appropriate treatment regimen should be used (see section 4.2).
F’ pazjenti li jkunu fuq terapija konkomitanti b’ lopinavir/ ritonavir, għandu jintuża l- programm ta ’ trattament li suppost jintuża (ara sezzjoni 4. 2).
Risk related to antiepileptic drugs in general
Riskju li ġeneralment għandu x’ jaqsam ma ’ mediċini anti- epilettiċi
Specialist advice should be given to women who are of childbearing potential.
Nisa li jista ’ jkollhom it- tfal għandhom jingħataw pariri ta ’ speċjalisti.
The need for treatment with AEDs should be reviewed when a woman is planning to become pregnant.
Il- ħtieġa għal trattament b’ AEDs għandha tiġi riveduta meta mara tkun qed tippjana biex toħroġ tqila.
In women being treated for epilepsy, sudden discontinuation of AED therapy should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child.
Nisa li jkunu qed jiġu trattati għal epilessija m’ għandhiex titwaqqfilhom f’ salt it- terapija b’ AEDs jekk possibbli għax dan jista ’ jwassal għal attakki mhux mistennija li jista ’ jkollhom konsegwenzi serji għall- mara u anke għat- tarbija.
The risk of congenital malformations is increased by a factor of 2 to 3 in the offspring of mothers treated with AEDs compared with the expected incidence in the general population of approximately 3%.
Ir- riskju ta ’ malformazzjonijiet konġenitali jiżdied b’ fattur ta ’ 2 sa 3 fil- wild ta ’ ommijiet trattati b’ AEDs meta mqabbel ma ’ l- inċidenza mistennija ta ’ 3% fil- popolazzjoni ġenerali.
The most frequently reported defects are cleft lip, cardiovascular malformations and neural tube defects.
Id- difetti l- aktar rappurtati ta ’ spiss huma cleft lip, malformazzjonijiet kardjo- vaskulari u difetti fit- tubu nevralġiku.
Therapy with multiple AEDs is associated with a higher risk of congenital malformations than monotherapy and therefore monotherapy should be used whenever possible.
Terapija b’ numru ta ’ AEDs hi assoċjata ma ’ riskju akbar ta ’ malformazzjonijiet konġenitali minn monoterapija u għalhekk meta possibbli għandha tintuża monoterapija.
62 Risk related to lamotrigine
66 Riskju relatat ma ’ lamotrigine
Pregnancy Epidemiological studies involving in total approximately 2000 women exposed to lamotrigine monotherapy during pregnancy cannot exclude an increased risk for congenital malformations.
Tqala Studji epidemjoloġi li kienu jinvolvu madwar 2000 mara li kienu fuq monoterapija b’ lamotrigine waqt it - tqala ma jeskludux riskju akbar ta ’ malformazzjonijiet konġenitali.
One registry has reported an increased incidence of facial clefts.
Reġistru minnhom irrapporta żjieda fl - inċidenza ta ’ qsim fil- wiċċ.
Other data sets have not confirmed this finding.
Dan ma ġiex konfermat minn settijiet oħra ta ’ tagħrif.
Animal studies have shown developmental toxicity (see section 5.3).
Fi studji fuq annimali dehret tossiċita ’ fl- iżvilupp (ara sezzjoni 5. 3)
If therapy with Lamictal is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended.
Jekk tinħass il- ħtieġa ta ’ terapija b’ lamotrigine waqt it- tqala, għandha tingħata l- inqas doża ta ’ lamotrigine possibbli.
Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase and could therefore theoretically lead to an increased risk of embryofoetal damage by reducing folic acid levels (see section 4.4).
Lamotrigine għandu ftit effett ta ’ impeditur fuq dihydrofolic acid reductase u għalhekk jista ’ teoretikament iwassal għal riskju akbar ta ’ ħsara għall- fetu embrijoniku billi jnaqqas il- livelli ta ’ aċidu foliku (ara sezzjoni 4. 4).
Intake of folic acid when planning pregnancy and during early pregnancy may be considered.
Wieħed għandu jikkonsidra sew it- teħid ta ’ aċidu foliku meta tkun qed tiġi ppjanata tqala u fil- bidu tat - tqala.
Physiological changes during pregnancy may affect lamotrigine levels and/ or therapeutic effect.
Bidliet fiżjoloġiċi waqt it- tqala jista ’ jkollhom effett fuq il- livelli ta ’ lamotrigine u/ jew effett terapewtiku.
There have been reports of decreased lamotrigine plasma levels during pregnancy with a potential risk of loss of seizure control.
Ġie rappurtat tnaqqis fil- livelli ta ’ plasma fil- lamotrigine waqt it- tqala bil- possibilta ’ ta ’ riskju ta ’ telf ta ’ kontroll waqt xi attakk.
Therefore lamotrigine serum concentrations should be monitored before, during and after pregnancy, as well as shortly after birth.
Wara t- twelid il- livelli ta ’ konċentrazzjonijiet ta ’ lamotrigine fis- serum għandhom jiġu monitorjati qabel, waqt u wara t- tqala, kif ukoll għal ftit żmien wara t- twelid.
If necessary, the dose should be adapted to maintain the lamotrigine serum concentration at the same level as before pregnancy, or adapted according to clinical response.
Jekk hemm bżonn, id - doża għandha tiġi adattata biex il- konċentrazzjoni ta ’ lamotrigine fis- serum tinżamm fl- istess livelli ta ’ qabel it- tqala, jew skond ir- riżultat kliniku.
In addition, dose-related undesirable effects should be monitored after birth.
Barra dan, effetti mhux mixtieqa li jkunu relatati mad- doża għandhom ikunu monitorjati wara t- twelid.
Lactation Data indicate that lamotrigine passes into breast milk.
Treddigħ Informazzjoni disponibbli tindika li lamotrigine jgħaddi fil- ħalib tas- sider.
In some breast-fed infants, the serum concentrations of lamotrigine reached levels at which pharmacological effects may occur.
F’ xi trabi li jerdgħu, il - konċentrazzjonijiet ta ’ lamotrigine fis- serum laħqu livelli li fihom jistgħu jseħħu effetti farmakoloġiċi.
The potential benefits of breast-feeding should be weighed against the potential risk of adverse effects occurring in the infant.
Il- benefiċċji li jistgħu joħorġu mit- treddigħ għandhom jitqabblu mal- possibilta ’ ta ’ riskju ta ’ effetti ħżiena fit- tarbija.
Should a woman decide to breast-feed while on therapy with lamotrigine, the infant should be monitored for adverse effects.
Jekk mara tiddeċiedi li tredda ’ meta tkun fuq terapija b’ lamotrigine, it- tarbija għandha tkun monitorjata għal xi effetti ħżiena.
Fertility Animal experiments did not reveal impairment of fertility by lamotrigine (see section 5.3).
Fertilita ’ Esperimenti fuq annimali ma wrew ebda indeboliment ta ’ fertilita ’ b’ lamotrigine (ara sezzjoni 5. 3).
As there is individual variation in response to all AED therapy, patients taking Lamictal to treat epilepsy should consult their physician on the specific issues of driving and epilepsy.
Billi r- riżultat tat- terapija b’ AEDs ivarja bejn individwu u ieħor, pazjenti li jieħdu Lamictal biex jikkuraw l - epilessija għandhom ikellmu lit- tabib tagħhom dwar xi problemi speċifiċi li jolqtu s- sewqan u l- epilessija.
No studies on the effects on the ability to drive and use machines have been performed.
Ma saru ebda studji dwar l- effetti fuq il- ħila għas- sewqan u t- tħaddim ta ’ magni.
Two volunteer studies have demonstrated that the effect of lamotrigine on fine visual motor co-ordination, eye movements, body sway and subjective sedative effects did not differ from placebo.
Żewġ studji fuq voluntieri wrew li l- effett ta ’ lamotrigine fuq il- koordinament viżwali, fuq il- movimenti tal- għajnejn, fuq iċ- ċaqliq tal - ġisem u fuq l- effetti sedattivi suġġettivi ma kienx differenti minn plaċebo.
In clinical trials with lamotrigine adverse reactions of a neurological character such as dizziness and diplopia have been reported.
Fi provi kliniċi b’ lamotrigine ġew rappurtati reazzjonijiet ħżiena ta ’ karattru newroloġiku bħal sturdamenti, u diplopija.
Therefore, patients should see how Lamictal therapy affects them before driving or operating machinery.
Għalhekk, il - pazjenti għandhom jaraw sew x’ effett terapija b’ Lamictal jista ’ jkollha fuqhom qabel isuqu jew iħaddmu makkinarju.
The undesirable effects have been divided into epilepsy and bipolar specific sections based on the data currently available.
L- effetti mhux mixtieqa ġew imqassma f’ sezzjonijiet speċifiċi ta ’ epilessija u bi- polari fuq il- bażi ta ’ tagħrif disponibbli fil- mument.
However, both sections should be consulted when considering the overall safety profile of lamotrigine.
Madankollu, iż- żewġ sezzjonijiet għandhom jiġu meqjusa fil- konsiderazzjoni tal - profil ġenerali ta ’ sigurta ’ ta ’ lamotrigine.
The following convention has been utilised for the classification of undesirable effects: - Very common (> 1/ 10), common (> 1/ 100 ,< 1/10), uncommon (> 1/ 1000 ,< 1/100), rare (> 1/ 10,000, < 1/ 1000), very rare (< 1/ 10,000).
67 Is- sistema li ġejja ġiet utilizzata għall- klassifikazzjoni ta ’ effetti mhux mixtieqa: - Komuni ħafna (> 1/ 10), komuni (> 1/ 100, < 1/ 10), mhux komuni (> 1/ 1000, < 1/ 100), rari (> 1/ 10, 000, < 1/ 1000), rari ħafna (< 1/ 10, 000).
63 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull grupp ta ’ frekwenzi, effetti mhux mixtieqa jidhru skond il- gravita ’ tagħhom u jibdew minn dawk l - aktar serji.
haematological abnormalities including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis.
Disturbi fid- demm u fis- sistema limfatika Rari ħafna: anormalitajiet ematoloġiċi inklużi newtropenija, lewkopenija, anemija, tromboċitopenija, panċitopenija, anemija aplastika, agranuloċitożi.
Haematological abnormalities may or may not be associated with the hypersensitivity syndrome (see Immune system disorders**).
Anormalitajiet ematoloġiċi jistgħu ikunu assoċjati mas- sindrome ta ’ sensittivita ’ eċċessiva u jistgħu ma jkunux (ara Disturbi fis- sistema immuni **).
hypersensitivity syndrome** (including such symptoms as, fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver, disseminated intravascular coagulation, multi-organ failure).
sindrome ta ’ sensittivita ’ eċċessiva ** (inklużi sintomi bħal deni, limfadenopatija, edema fil - wiċċ, anormalitajiet fid- demm u fil- fwied, koagulazjoni intravaskulari mxerrda, ħsara f’ diversi organi tal- ġisem).
**Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema and abnormalities of the blood and liver.
** Raxx ġie rappurtat bħala parti mis- sindrome ta ’ sensittivita ’ eċċessiva assoċjata ma ’ għamla li tvarja ta ’ sintomi sistemiċi inklużi deni, limfadenopatija, edema fil- wiċċ, u anormalitajiet fid- demm u fil- fwied.
The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation and multiorgan failure.
Is- sindrome turi firxa wiesgħa ta ’ severita ’ klinika u, rarament, tista ’ twassal għal koagulazzjoni intravaskulari mxerrda u ħsara f’ diversi organi tal- ġisem.
It is important to note that early manifestations of hypersensitivity (for example fever, lymphadenopathy) may be present even though rash is not evident.
Importanti wieħed ikun jaf li jista ’ jkun hemm sinjali bikrin ta ’ sensittivita ’ eċċessiva (per eżempju deni, limfadenopatija) minkejja li ma jkunx hemm raxx.
If such signs and symptoms are present, the patient should be evaluated immediately and Lamictal discontinued if an alternative aetiology cannot be established.
Jekk ikun hemm sinjali u sintomi bħal dawn, il- pazjent għandu jiġi evalwat immedjatament u Lamictal jitwaqqaf jekk ma tkunx tista ’ tiġi stabbilita etjoloġija oħra.
aggression, irritability. confusion, hallucinations, tics.
aggressjoni, irritabilita ’ taħwid, alluċinazzjonijiet, tagħwiġ involuntarju ta ’ muskoli.
Nervous system disorders During monotherapy clinical trials:
Disturbi fis- sistema
Very common:
nervuża
Common:
Komuni ħafna: uġigħ ta ’ ras Komuni:
Rare:
nagħas, sturdamenti, rogħda, insomnja.
headache. somnolence, dizziness, tremor, insomnia. ataxia. nystagmus.
Mhux komuni: atassija Rari: nistagmus
During other clinical experience:
Matul esperjenza oħra klinika:
somnolence, ataxia, dizziness, headache. nystagmus, tremor, insomnia. agitation, unsteadiness, movement disorders, worsening of Parkinson's disease, extrapyramidal effects, choreoathetosis, increase in seizure frequency.
nagħas, atassija, sturdament, uġigħ ta ’ ras nistagmus, rogħda, insomnja. aġitazzjoni, nuqqas ta ’ stabbilita ’, disturbi tal- moviment, peġġjorament tal- marda Parkinson, effetti strapiramidali, koreoatetożi, żjieda fil- frekwenza ta ’ aċċessjonijiet.
There have been reports that lamotrigine may worsen parkinsonian symptoms in patients with pre-existing Parkinson’ s disease, and isolated reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition.
Xi rapporti wrew li lamotrigine jista ’ jħażżen is- sintomi tal- marda Parkinson f’ pazjenti li ġa kienu jbatu b’ dil- marda, u xi każi iżolati ta ’ effetti strapiramidali u koreoatetożi f’ pazjenti li ma kienux ibatu minn dil- kondizzjoni.
Eye disorders During monotherapy clinical trials:
Disturbi fl- għajnejn Waqt provi kliniċi b’ monoterapija:
Uncommon:
Mhux komuni: diplopija, vista mċajpra
diplopia, blurred vision.
Minn esperjenza oħra klinika:
Very common:
68 Komuni ħafna:
diplopia, blurred vision. conjunctivitis.
diplopija, vista mċajpra. konġuntivite
Gastrointestinal disorders During monotherapy clinical trials:
Disturbi gastro- intestinali Waqt provi kliniċi b’ monoterapija:
64 Common:
Komuni:
nausea, vomiting, diarrhoea.
dardir, remettar, dijareja.
During other clinical experience:
Minn esperjenza oħra klinika:
nausea, vomiting. diarrhoea.
dardir, remettar. dijareja
hepatic failure, hepatic dysfunction, increased liver function tests.
nuqqas ta ’ funzjonament tal- fwied, funzjonament batut tal- fwied, żjieda ta ’ testijiet għall- funzjonament tal- fwied.
Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.
Funzjonament batut tal- fwied normalment jiġri f’ assoċjazzjoni ma ’ reazzjonijiet ta ’ sensittivita ’ eċċessiva biss ġie li kien hemm każijiet iżolati bla ebda sinjali ċari ta ’ sensittivita ’ eċċessiva.
Very rare:
Rari Rari ħafna:
Stevens– Johnson Syndrome. toxic epidermal necrolysis.
raxx fil- ġilda Sindrome Stevens- Johnson nekroliżi tossika tal- ġilda.
The skin rashes led to the withdrawal of lamotrigine treatment in 2% of patients.
Fi provi kliniċi addizzjonali u double- blind fuq adulti, żviluppaw każijiet ta ’ raxx fil- ġilda sa fuq 10% ta ’ pazjenti li kienu jieħdu lamotrigine u sa fuq 5% f’ pazjenti fuq plaċebo.
The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of Lamictal (see section 4.4).
Ir- raxx, li normalment ikun jidher ta ’ għamla makulopapulari, ġeneralment jitfaċċa matul l- ewwel tmien ġimgħat minn mindu jinbeda t- trattament u jgħaddi malli Lamictal jitwaqqaf (ara sezzjoni 4. 4).
Serious potentially life-threatening skin rashes, including Stevens– Johnson syndrome and toxic epidermal necrolysis (Lyell’ s Syndrome) have been reported.
Ġew irrappurtati każijiet serji ta ’ raxx fil- ġilda ta ’ periklu għall- ħajja, inklużi s- sindrome Stevens- Johnson u nekroliżi tossika tal- ġilda (Sindrome ta ’ Lell).
Although the majority recover on withdrawal of lamotrigine treatment, some patients experience irreversible scarring and there have been rare cases of associated death (see section 4.4).
Għalkemm il- biċċa l- kbira jirkupraw malli lamotrigine jitwaqqaf, xi pazjenti iġarrbu ċikatriċi irreversibbli u kien hemm ukoll każijiet ta ’ mwiet assoċjati ma ’ dan (ara sezzjoni 4. 4).
The overall risk of rash, appears to be strongly associated with:
Ir- riskju ta ’ raxx jidher li jkun relatat ħafna ma ’:
- high initial doses of lamotrigine and exceeding the recommended dose escalation of
- dożi qawwija ta ’ lamotrigine fil- bidu li jeċċedu ż- żidiet rakkomandati fit- terapija
lamotrigine therapy (see section 4.2)
b’ lamotrigine (ara sezzjoni 4. 2)
- concomitant use of valproate (see section 4.2).
- l- użu ta ’ valproate fl- istess ħin (ara sezzjoni 4. 2).
Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms (see Immune system disorders**).
Raxx ġie wkoll rappurtat bħala parti mis- sindrome ta ’ sensittivita ’ eċċessiva assoċjata ma ’ għamla varjabbli ta ’ sintomi sistemiċi (ara Disturbi fis- sistema immuni **).
Musculoskeletal and connective tissue disorders Very rare:
Disturbi muskulo- skeletriċi u tal- connective tissue Rari ħafna:
lupus-like reactions.
reazzjonijiet qieshom ta ’ lupus.
General disorders Common:
Disturbi ġenerali Komuni:
and administration site conditions tiredness.
u kondizzjonijiet ta ’ mnejn jingħata għeja.
Bipolar Disorder
Mard Bi- polari
The undesirable effects below should be considered alongside those seen in epilepsy for an overall safety profile of lamotrigine.
L- effetti mhux mixtieqa li jidhru hawn taħt għandhom jiġu kkunsidrati flimkien ma ’ dawk li jidhru fl- epilessija fil- profil ta ’ sigurta ’ ġenerali ta ’ lamotrigine
Nervous system disorders During bipolar disorder clinical trials:
69 Waqt provi kliniċi dwar mard bi- polari:
headache. agitation, somnolence, dizziness.
aġitazzjoni, nagħas, sturdamenti.
Gastrointestinal disorders During bipolar disorder clinical trials:
Disturbi gastro- intestinali Waqt provi kliniċi dwar mard bi- polari:
dry mouth
ħalq xott
Very common:
Disturbi fil- ġilda Waqt provi kliniċi Komuni ħafna:
Stevens– Johnson Syndrome.
u fit- tessuti ta ’ taħt il- ġilda dwar mard bi- polari: raxx fil- ġilda Sindrome Stevens- Johnson.
When all bipolar disorder studies (controlled and uncontrolled) conducted with lamotrigine are considered, skin rashes occurred in 12% of patients on lamotrigine.
Meta jiġu kkunsidrati l- istudji kollha dwar mard bi- polari (kontrollati u mhux kontrollati) li saru b’ lamotrigine, raxx fil- ġilda seħħ fi 12% ta ’ pazjenti fuq lamotrigine.
Whereas, in controlled clinical trials with bipolar disorder patients, skin rashes occurred in 8% of patients taking lamotrigine and in 6% of patients taking placebo.
Waqt li, fi provi kliniċi kontrollati fuq pazjenti b’ mard bi- polari, raxx fil- ġilda seħħ fi 8% ta ’ pazjenti fuq lamotrigine u f’ 6% ta ’ pazjenti fuq plaċebo.
Musculoskeletal and connective tissue disorders During bipolar disorder clinical trials:
Disturbi muskulo- skeletriċi u tal- connective tissue Waqt provi kliniċi dwar mard bi- polari:
arthralgia.
artralġija
General disorders and administration site conditions During bipolar disorder clinical trials:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Waqt provi kliniċi dwar mard bi- polari:
pain, back pain.
uġigħ, uġigħ fid- dahar.
Symptoms and signs
Sintomi u sinjali
Acute ingestion of doses in excess of 10 to 20 times the maximum therapeutic dose has been reported.
Ġew rappurtati każijiet fejn ittieħdu 10 sa 20 darba aktar mid- doża massima terapewtika.
Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness and coma.
Teħid ta ’ doża eċċessiva rriżultat f’ sintomi bħal nistagmus, ataksija, disturbi tas- sensi u koma.
In the event of overdosage, the patient should be admitted to hospital and given appropriate supportive therapy.
Fil- każ ta ’ dożaġġ żejjed, il- pazjent għandu jittieħed l- isptar u jingħata l- kura ta ’ sapport adatta.
Therapy aimed at decreasing absorption (activated charcoal, laxative or gastric lavage) should be performed if indicated.
Għandha ssir terapija bil- għan li tnaqqas l- assorbiment (faħam ta ’ l- injam attivat, lassativ jew lavanda gastrika) jekk indikata.
There is no experience with haemodialysis as treatment of overdose.
Ma hemmx tagħrif dwar każi ta ’ emodijalisi bħala trattament għal doża eċċessiva.
In six volunteers with kidney failure, 20% of the lamotrigine was removed from the body during a 4-hour haemodialysis session (see section 5.2).
F’ sitt voluntieri f’ saħħithom li kellhom indeboliment tal- kliewi, tneħħa 20% ta ’ lamotrigine mill- ġisem waqt sessjoni ta ’ 4 sigħat emodijalisi (ara sezzjoni 5. 2).
N03AX09.
Grupp farmakoterapewtiku: anti- epilettiċi oħra, kodiċi ATC: N03AX09.
The results of pharmacological studies suggest that lamotrigine is a use- and voltage-dependent blocker of voltage gated sodium channels.
Ir- riżultati minn studji farmakoloġiċi jindikaw li lamotrigine hu imblokkatur dipendenti minn użu u voltaġġ ta ’ kanali tas- sodju voltage gated.
It inhibits sustained repetitive firing of neurones and inhibits release of glutamate (the neurotransmitter which plays a key role in the generation of epileptic seizures).
Hu jinibixxi l- isparar repetitiv ta ’ newroni u jimpedixxi l- ħruġ ta ’ glutamat (in- newrotrasmettitur li għandu parti importanti ħafna fil- ġenerazzjoni ta ’ attakki epilettiċi).
These effects are likely to contribute to the anticonvulsant properties of lamotrigine.
Dawn l- effetti x’ aktarx jikkontribwixxu għall- kwalita ’ anti- konvulsiva ta ’ lamotrigine.
In contrast, the mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established, although interaction with voltage gated sodium channels is likely to be important.
70 Minn naħa l- oħra, ma ġewx stabbiliti l- mekkaniżmi li permezz tagħhom lamotrigine jeżerċita l- azzjoni terapewtika tiegħu f’ mard bi- polari, għalkemm l- interazzjoni ma ’ kanali tas- sodju voltage gated aktarx fiha l- importanza tagħha.
66 placebo, whereas both 1000 mg phenytoin and 10 mg diazepam each significantly impaired fine visual motor co-ordination and eye movements, increased body sway and produced subjective sedative effects.
F’ testijiet maħsuba biex jiġu evalwati l- effetti fis- sistema nervuża ċentrali ta ’ prodotti mediċinali, ir- riżultati miksuba minn użu ta ’ dożi ta ’ 240 mg lamotrigine mogħtija lil voluntieri f’ saħħithom ma kienux differenti minn dawk bi plaċebo, waqt li 1000 mg phenytoin u 10 mg diazepam it- tnejn kemm huma ikkawżaw indeboliment sinifikanti fil- koordinament tal- mutur viżwali u l- movimenti ta ’ l- għajnejn, żiedu fit- tbandil tal- ġisem u pproduċew effetti sedattivi suġġettivi.
In another study, single oral doses of 600 mg carbamazepine significantly impaired fine visual motor co-ordination and eye movements, while increasing both body sway and heart rate, whereas results with lamotrigine at doses of 150 mg and 300 mg did not differ from placebo.
Fi studju ieħor, dożi orali waħedhom ta ’ 600 mg carbamazepine ikkawżaw indeboliment sinifikanti fil - koordinament tal- mutur viżwali u l- movimenti ta ’ l- għajnejn, waqt li żiedu kemm it- tbandil tal- ġisem u kemm it- taħbit tal- qalb, filwaqt li riżultati b’ dożi ta ’ 150 mg u 300 mg lamotrigine ma wrewx differenza minn plaċebo.
Clinical efficacy and safety in children aged 1 to 24 months
Effikaċja klinika u sigurta ’ fit- tfal ta ’ eta ’ minn 1 sa 24 xahar
The efficacy and safety of adjunctive therapy in partial seizures in patients aged 1 to 24 months has been evaluated in a small double-blind placebo-controlled withdrawal study.
L- effikaċja u sigurta ’ ta ’ terapija aġġuntiva f’ aċċessjonijiet parzjali f’ pazjenti ta ’ eta ’ minn 1 sa 24 xahar ġiet evalwata fi studju żgħir, double- blind, ikkontrollat bi plaċebo, irtirat.
Treatment was initiated in 177 subjects, with a dose titration schedule similar to that of children aged 2 to 12 years.
Inbdiet il- kura f’ 177 suġġett bi skeda ta ’ titrazzjoni tad- doża simili ta ’ dik fi tfal ta ’ bejn is- 2 u t- 12- il sena.
Lamotrigine 2 mg tablets are the lowest strength available, therefore the standard dosing schedule was adapted in some cases during the titration phase (for example, by administering a 2 mg tablet on alternate days when the calculated dose was less than 2 mg).
Il- pilloli ta ’ lamotrigine ta ’ 2mg huma l- aktar doża baxxa disponibbli, għalhekk l- iskeda ta ’ dożaġġ standard kienet aġġornata f' xi każijiet waqt il- fażi ta ’ titrazzjoni (per eżempju billi tagħti pillola ta ’ 2mg ġurnata iva u oħra le meta d- doża kkalkulata kienet ta ’ anqas minn 2mg).
Serum levels were measured at the end of week 2 of titration and the subsequent dose either reduced or not increased if the concentration exceeded 0.41 µg/ mL, the expected concentration in adults at this time point.
Il- livelli fis- serum kienu mkejla fl- aħħar ta ’ ġimgħa 2 tat- titrazzjoni u d- doża ta ’ wara jew imnaqqsa jew mhux miżjuda jekk il- konċentrazzjoni kienet ta’ aktar minn 0. 41µg/ mL, il- konċentrazzjoni mistennija fl- adulti f’ dan il- punt.
Dose reductions of up to 90% were required in some patients at the end of week 2.
Kien hemm bżonn ta ’ tnaqqis fid- doża sa 90% f’ xi pazjenti fl- aħħar ta ’ gimgħa 2.
Thirty-eight responders (> 40% decrease in seizure frequency) were randomised to placebo or continuation of lamotrigine.
Tmienja u tletin minn dawk li rrispondew (> 40% tnaqqis fil- frekwenza ta 'aċċessjonijiet) ġew imqassma bl- addoċċ jew għal plaċebo jew inkella jkomplu fuq lamotrigine.
The proportion of subjects with treatment failure was 84% (16/ 19 subjects) in the placebo arm and 58% (11/ 19 subjects) in the lamotrigine arm.
Il - proporzjon ta ’ suġġetti b’ falliment fil- kura kien ta ’ 84% (16/ 19 suġġetti) fil- fergħa tal- plaċebo u 58% (11/ 19 suġġetti) fil- fergħa ta ’ lamotrigine.
The difference was not statistically significant:
Din id- differenza ma kienetx statistikament sinifikanti:
26.3%, CI95% -2.6 %< > 50.2%, p=0.07.
26. 3%, CI95% - 2. 6% < > 50. 2%, p=0. 07.
A total of 256 subjects between 1 to 24 months of age have been exposed to lamotrigine in the dose range 1 to 15 mg/ kg/ day for up to 72 weeks.
Total ta ’ 256 suġġett ta ’ bejn 1 u 24 xahar kien espost għal lamotrigine f’ doża li tvarja bejn 1 u 15mg/ kg/ kuljum sa 72 ġimgħa.
The safety profile of lamotrigine in children aged 1 month to 2 years was similar to that in older children except that clinically significant worsening of seizures (> =50%) was reported more often in children under 2 years of age (26%) as compared to older children (14%).
Il- profil ta ’ sigurta ’ ta ’ lamotrigine fit- tfal minn xahar sa sentejn kienet simili għal dak fi tfal akbar barra li żvilupp klinikament sinifikanti għall- agħar ta ’ aċċessjonijiet (> =50%) kienet rappurtata aktar spiss fi tfal taħt is- sentejn (26%) meta mqabbla ma ’ tfal akbar (14%).
Clinical efficacy and safety in Lennox-Gastaut syndrome
Effikaċja klinika u sigurta ’ fis- sindrome ta ’ Lennox- Gastaut
There are no data for monotherapy in seizures associated with Lennox-Gastaut syndrome.
Ma hemmx data fuq monoterapija f’ aċċessjonijiet assoċjata mas- sindrome ta ’ Lennox- Gastaut.
Clinical efficacy in the prevention of mood episodes in patients with bipolar disorder
Effikaċja klinika fil- prevenzjoni ta ’ episodji ta ’ buri f’ pazjenti b’ mard bi- polari
The efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder has been evaluated in two studies.
L- effikaċja ta ’ lamotrigine fil- prevenzjoni ta ’ episodji ta ’ bdil fil- burdata f’ pazjenti b’ disturbi bi- polari I kienet evalwata f’ żewġ studji.
Study SCAB2003 was a multicentre, double-blind, double dummy, placebo and lithium-controlled, randomised fixed dose evaluation of the long-term prevention of relapse and recurrence of depression and/ or mania in patients with bipolar I disorder who had recently or were currently experiencing a major depressive episode.
L- istudju SCAB2003 kien f’ aktar minn ċentru wieħed, double- blind, double dummy, ikkontrollat bi plaċebo u lithium, intagħżel bl- addoċċ l- evalwazzjoni tad- doża fissa għal prevenzjoni fit- tul ta ’ rkadenza u rikorrenza ta ’ dipressjoni u/ jew mania f’ pazjenti b’ disturb bi- polari I li kellhom riċentement jew kienu qed jesperjenzaw episodju ta ’ dipressjoni maġġuri.
Once stabilised using lamotrigine monotherapy or adjunctive therapy, patients were randomly assigned into one of five treatment groups: lamotrigine (50, 200, 400 mg/ day), lithium (serum levels of 0.8 to 1.1 mMol/ L) or placebo for a maximum of 76 weeks (18 months).
La darba stabbiliti b’ monoterapija b’ lamotrigine jew terapija aġġuntiva, il- pazjenti ġew imqassma bl- addoċċ f’ wieħed mill- ħames gruppi ta ’ kura: lamotrigine (50, 200, 400mg/ kuljum, lithium (livelli fis- serum ta '0. 8 sa 1. 1 mMol/ L) jew plaċebo għal massimu ta' 76 ġimgħa (18- il xahar).
The primary endpoint was "Time to Intervention for a Mood Episode (TIME)", where the interventions were additional pharmacotherapy or electroconvulsive therapy (ECT).
L- istudju
Study SCAB2006 had a similar design as study SCAB2003, but differed from study SCAB2003 in evaluating a flexible dose of lamotrigine (100 to 400 mg/ day) and including patients with bipolar I disorder who had recently or were currently experiencing a manic episode.
Ir- riżultati jidhru f’ Tabella 7.
The results are shown in Table 7.
Tabella 7:
Summary of results from studies investigating the efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder
Sommarju ta ’ riżultati minn studji li jinvestigaw l- effikaċja ta ’ lamotrigine fil- prevenzjoni ta ’ episodji ta ’ mania f’ pazjenti b’ disturb bi- polari I
‘ Proportion’ of patients being event free at week 76
‘ Proporzjon ’ ta ’ pazjenti li kienu liberi minn eventi f’ ġimgħa 76
Study SCAB2003 Bipolar I
Studju SCAB2003 Bi- polari I
Study SCAB2006 Bipolar I
Studju SCAB2006 Bi- polari I
Inclusion criterion
Kriterju ta ’ inklużjoni
Major depressive episode
Episodju ta ’ dipressjoni maġġuri
Major manic episode
Episodju ta ’ mania maġġuri
Lamotrigine Lithium
Lamotrigine
Placebo Lamotrigine Lithium
Plaċebo Lamotrigine Lithium
Intervention free p-value Log rank test
Liberi minn intervent p- value Log rank test
0.22 0.21 0.004 0.006
0. 21 0. 006
0.12 0.17 0.24 - 0.023 0.006
0. 12 0. 17 0. 24 - 0. 023 0. 006
0.04 -
0. 04 -
Depression free
Liberi minn dipressjoni
0.51 0.46
0. 51
0.41 0.82
0. 46
0.71
0. 41 0. 82 0. 71
p-value Log rank
p- value Log rank test
0.047
0. 047
0.209 -
0. 209
-value Log rank 0.047 0.209 -
Liberi minn mania
0.015
0. 70
0.167
0. 86
-
0. 67
test
0. 53
Free of mania p-value Log rank test
0. 64
0.70 0.339
0. 37
0.86 0.026
- value Log rank test
0.67 -
0. 339
0.53 0.280
0. 026 -
0.64 0.006
0. 280
0.37 -
0. 006
In supportive analyses of time to first depressive episode and time to first manic/ hypomanic or mixed episode, the lamotrigine-treated patients had significantly longer times to first depressive episode than placebo patients, and the treatment difference with respect to time to manic/ hypomanic or mixed episodes was not statistically significant.
F’ analiżi ta ’ sapport ta ’ żmien sa l- ewwel episodju dipressiv u żmien sa l- ewwel episodju ta ’ mania/ ipomania jew episodji mħallta, il- pazjenti ttrattati b’ lamotrigine kellhom żminijiet ħafna itwal għall - ewwel episodju ta ’ dipressjoni minn pazjenti fuq plaċebo, u d- differenza fil- kura fejn jidħol iż- żmien għal episodji ta ’ mania/ ipomanija jew imħallta ma ’ kienx statistikament sinifikanti.
The efficacy of lamotrigine in combination with mood stabilisers has not been adequately studied.
L- effikaċja ta ’ lamotrigine flimkien ma ’ mood stabilisers ma kienx studjat b' mod adekwat.
Suicidality analysis
Analiżi ta ’ suwiċidalita ’
The incidence of suicidal ideation and behaviour was evaluated in a pooled analysis of placebo-controlled clinical trials with lamotrigine involving a total of 6467 patients from a number of indications.
l- inċidenza ta ’ ideazzjoni u aġir suwiċidali kienet evalwata f’ analiżi miġbura flimkien ta ’ studji kliniċi kkontrollati bi plaċebo b’ lamotrigine li fihom kienu involuti total ta ’ 6467 pazjent minn numru ta ’ indikazzjonijiet.
In the subset of bipolar disorder trials, the rate of events was numerically, but not statistically significantly, greater for lamotrigine (29/ 1212 [2.4%]) compared with placebo (19/ 1054 [1.8%]).
F’ subset ta ’ studji kliniċi fuq disturbi bi- polari, ir- rata ta ’ eventi kienet numerikament, iżda mhux statistikament sinifikament, akbar għal lamotrigine (29/ 1212 [2. 4%] meta mqabbla ma ’ plaċebo (19/ 1014 [1. 8%].
In a pooled analysis of psychiatric indications, events were more common in the first month of treatment, in patients taking lamotrigine.
F’ analiżi miġbura flimkien ta ’ indikazzjonijiet psikjatriċi, l- eventi kienu aktar komuni fl- ewwel xahar ta ’ trattament, f’ pazjenti li kienu qed jieħdu lamotrigine.
Behavioural events were more common in males.
Eventi li jinvolvu l- aġir kienu aktar komuni fl- irġiel.
In the subset of epilepsy trials, there were no statistically significant differences in the rate of events between lamotrigine and placebo.
Fis- subset ta ’ studji kliniċi ta ’ epilessija, ma kienx hemm differennzi statistikament sinifikanti fir- rati ta ’ eventi bejn lamotrigine u plaċebo.
Although the number of suicidal ideation and behaviour events was too low (6/ 1073 [0.6%] on lamotrigine and 2/ 805 [0.3%] on placebo) to allow a definitive comparison between treatment groups, the relative rate reported from this lamotrigine analysis is consistent with the reported class effect for AEDs (see section 4.4).
Għalkemm in- numru ta ’ ideazzjoni suwiċidali u eventi li jinvolvu l- aġir kienu baxxi wisq (6/ 1073 [0. 6%] fuq lamotrigine u 2/ 805 [0. 3%] fuq plaċebo) biex iħallu tqabbil definittiv bejn il- gruppi ta ’ kura, ir- rata relattiva irrapurtata minn din l- analiżi ta ’ lamotrigine hija konsistenti ma ’ l - effett ta ’ klassi irrapurtat għall- AED (ara s- sezzjoni 4. 4).
Study of the effect of lamotrigine on cardiac conduction
Studju dwar l- effett ta ’ lamotrigine fuq trasmissjoni kardijaka
A study in healthy adult volunteers evaluated the effect of repeat doses of lamotrigine (up to 400 mg/ day) on cardiac conduction, as assessed by 12-lead ECG.
Studju fuq voluntieri adulti f’ saħħithom evalwa l- effett ta ’ dożi ripetuti ta ’ lamotrigine ((sa 400 mg/ kuljum) fuq trasmissjoni kardijaka, kif assessjat bi 12- lead ECG.
There was no clinically significant effect of lamotrigine on QT interval compared to placebo.
Ma kien hemm ebda effett klinikament sinifikanti ta ’ lamotrigine fuq intervall QT meta mqabbel ma ’ plaċebo.
68 5.2 Pharmacokinetic properties
72 5. 2 Tagħrif farmakokinetiku
Lamotrigine is rapidly and completely absorbed from the gut with no significant first-pass metabolism.
Lamotrigine jiġi assorbit malajr u kompletament mill- imsaren mingħajr ebda metaboliżmu first- pass sinifikanti.