natgillin/translations-raw huggingface dataset:
62 de 14 frivillige somnolens sammenlignet med 1 ud af 20, når risperidon blev administreret alene, og ingen, når lamotrigin blev administreret alene.
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.
Forsøg in vitro tydede på, at dannelsen af lamotrigins primære metabolit, 2- N- glukuronid, blev hæmmet minimalt ved samtidig inkubation med amitriptylin, bupropion, clonazepam, haloperidol eller lorazepam.
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.
Disse forsøg tydede også på, at metaboliseringen af lamotrigin sandsynligvis ikke hæmmes af clozapin, fluoxetin, phenelzin, risperidon, sertralin eller trazodon.
These experiments also suggested that metabolism of lamotrigine was unlikely to be inhibited by clozapine, fluoxetine, phenelzine, risperidone, sertraline or
Effekten af hormonale kontraceptiva på lamotrigins farmakokinetik I et forsøg med 16 frivillige kvinder medførte brug af en kombineret peroral antikonceptionspille med 30 µg ethinyløstradiol/ 150 µg levonorgestrel ca. en fordobling af den perorale clearance af lamotrigin, hvilket resulterede i en gennemsnitlig reduktion af AUC og Cmax af lamotrigin på henholdsvis 52% og 39%.
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.
4. 4).
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).
4. 2).
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).
Effekten af lamotrigin på hormonale kontraceptivas farmakokinetik I et forsøg med 16 frivillige kvinder havde en steady state- dosis på 300 mg lamotrigin ingen effekt på farmakokinetikken af ethinyløstradiol- komponenten i en kombineret peroral antikonceptionspille.
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.
Der blev observeret en beskeden stigning i den perorale clearance af levonorgestrel- komponenten, hvilket medførte et gennemsnitligt fald i AUC og Cmax af levonorgestrel på henholdsvis 19% og 12%.
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.
Effekten af andre doser lamotrigin end 300 mg dagligt er ikke blevet undersøgt, og der er ikke foretaget forsøg med andre hormonpræparater til kvinder.
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.
4. 2).
In patients receiving concomitant therapy with rifampicin, the appropriate treatment regimen should be used (see section 4.2).
I et forsøg med raske frivillige forsøgspersoner blev plasmakoncentrationen af lamotrigin omtrent halveret ved brug af lopinavir/ ritonavir, muligvis på grund af induktion af glukuronidering.
In a study in healthy volunteers, lopinavir/ ritonavir approximately halved the plasma concentrations of lamotrigine, probably by induction of glucuronidation.
4. 2).
In patients receiving concomitant therapy with lopinavir/ ritonavir, the appropriate treatment regimen should be used (see section 4.2).
3% hos den almene befolkning.
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%.
Risici i forbindelse med lamotrigin
62 Risk related to lamotrigine
2. 000 kvinder, som under graviditeten blev eksponeret for monoterapi med lamotrigin, kan det ikke udelukkes, at der er en øget risiko for medfødte misdannelser.
Pregnancy Epidemiological studies involving in total approximately 2000 women exposed to lamotrigine monotherapy during pregnancy cannot exclude an increased risk for congenital malformations.
5. 3).
Animal studies have shown developmental toxicity (see section 5.3).
4. 4).
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).
Fysiologiske forandringer under graviditeten kan påvirke niveauerne og/ eller den terapeutiske effekt af lamotrigin.
Physiological changes during pregnancy may affect lamotrigine levels and/ or therapeutic effect.
Amning Data tyder på, at lamotrigin udskilles i modermælk.
Lactation Data indicate that lamotrigine passes into breast milk.
5. 3).
Fertility Animal experiments did not reveal impairment of fertility by lamotrigine (see section 5.3).
I kliniske forsøg med lamotrigin er der rapporteret om bivirkninger af neurologisk karakter, f. eks. svimmelhed og diplopi.
In clinical trials with lamotrigine adverse reactions of a neurological character such as dizziness and diplopia have been reported.
64 4. 8 Bivirkninger
4.8 Undesirable effects
Følgende benævnelser er anvendt til klassificering af bivirkninger: meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 til < 1/ 10), ikke almindelig (≥ 1/ 1. 000 til < 1/ 100), sjælden (≥ 1/ 10. 000 til < 1/ 1. 000), meget sjælden (< 1/ 10. 000).
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).
De alvorligste bivirkninger er anført først.
63 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Hæmatologiske abnormiteter, herunder neutropeni, leukopeni, anæmi, trombocytopeni, pancytopeni, aplastisk anæmi, agranulocytose.
haematological abnormalities including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis.
Hæmatologiske abnormiteter kan være forbundet med overfølsomhedssyndrom (se Immunsystemet **).
Haematological abnormalities may or may not be associated with the hypersensitivity syndrome (see Immune system disorders**).
Overfølsomhedssyndrom ** (herunder symptomer som feber, lymfadenopati, ansigtsødem, blod - og leverabnormiteter, dissemineret intravaskulær koagulation, multiorgansvigt).
hypersensitivity syndrome** (including such symptoms as, fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver, disseminated intravascular coagulation, multi-organ failure).
** Der er også rapporteret om udslæt som en del af et overfølsomhedssyndrom, der er forbundet med et skiftende mønster af systemiske symptomer, herunder feber, lymfadenopati, ansigtsødem samt blod - og leverabnormiteter.
**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.
Konfusion, hallucinationer, tics.
aggression, irritability. confusion, hallucinations, tics.
Under kliniske forsøg med monoterapi:
Nervous system disorders During monotherapy clinical trials:
Nystagmus.
headache. somnolence, dizziness, tremor, insomnia. ataxia. nystagmus.
Ved anden klinisk erfaring:
During other clinical experience:
Agitation, usikkerhed på benene, bevægeforstyrrelser, forværring af Parkinsons sygdom, ekstrapyramidale effekter, choreoathetosis, stigning i frekvensen af krampeanfald.
somnolence, ataxia, dizziness, headache. nystagmus, tremor, insomnia. agitation, unsteadiness, movement disorders, worsening of Parkinson's disease, extrapyramidal effects, choreoathetosis, increase in seizure frequency.
Der foreligger rapporter om, at lamotrigin kan forværre symptomer på Parkinsons sygdom hos patienter med eksisterende Parkinsons sygdom, og der er enkeltstående rapporter om ekstrapyramidale effekter og choreoathetosis hos patienter uden denne grundsygdom.
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.
65 Øjne Under kliniske forsøg med monoterapi:
Eye disorders During monotherapy clinical trials:
Conjunctivitis.
diplopia, blurred vision. conjunctivitis.
Under kliniske forsøg med monoterapi:
Gastrointestinal disorders During monotherapy clinical trials:
Almindelig:
64 Common:
Diarré.
nausea, vomiting. diarrhoea.
Meget sjælden:
Hepato-biliary disorders Very rare:
Hududslæt.
skin rash.
Toksisk epidermal nekrolyse.
Stevens– Johnson Syndrome. toxic epidermal necrolysis.
I dobbeltblindede kliniske forsøg med tillægsbehandling hos voksne forekom der udslæt hos op til 10% af de patienter, som fik lamotrigin, og hos 5% af de patienter, som fik placebo.
In double-blind, adjunctive clinical trials in adults, skin rashes occurred in up to 10% of patients taking lamotrigine and in 5% of patients taking placebo.
Hududslættene førte til seponering af behandlingen med lamotrigin hos 2% af patienterne.
The skin rashes led to the withdrawal of lamotrigine treatment in 2% of patients.
4. 4).
The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of Lamictal (see section 4.4).
Der er rapporteret om alvorlige, potentielt livstruende udslæt, herunder Stevens- Johnsons syndrom og toksisk epidermal nekrolyse (Lyells syndrom).
Serious potentially life-threatening skin rashes, including Stevens– Johnson syndrome and toxic epidermal necrolysis (Lyell’ s Syndrome) have been reported.
4. 4).
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).
- Høj initialdosis og overskridelse af den anbefalede dosisøgning af lamotrigin (se pkt.
- high initial doses of lamotrigine and exceeding the recommended dose escalation of
4. 2)
lamotrigine therapy (see section 4.2)
4. 2).
- concomitant use of valproate (see section 4.2).
Der er også rapporteret om udslæt som en del af et overfølsomhedssyndrom forbundet med et skiftende mønster af systemiske symptomer (se Immunsystemet **).
Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms (see Immune system disorders**).
Almene symptomer og reaktioner på administrationsstedet Almindelig:
General disorders Common:
Træthed.
and administration site conditions tiredness.
66 Nervesystemet Under kliniske forsøg vedrørende bipolar sygdom:
Nervous system disorders During bipolar disorder clinical trials:
Agitation, somnolens, svimmelhed.
headache. agitation, somnolence, dizziness.
Under kliniske forsøg vedrørende bipolar sygdom:
Gastrointestinal disorders During bipolar disorder clinical trials:
Mundtørhed.
dry mouth
Hud og subkutane væv
65
Under kliniske forsøg vedrørende bipolar sygdom:
Skin and subcutaneous tissue disorders During bipolar disorder clinical trials:
Stevens- Johnsons syndrom.
Stevens– Johnson Syndrome.
udført med lamotrigin, forekom der hududslæt hos 12% af de patienter, som fik lamotrigin.
When all bipolar disorder studies (controlled and uncontrolled) conducted with lamotrigine are considered, skin rashes occurred in 12% of patients on lamotrigine.
Derimod forekom der i kontrollerede kliniske forsøg hos patienter med bipolar sygdom hududslæt hos 8% af de patienter, som fik lamotrigin, og hos 6% af de patienter, som fik placebo.
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.
Knogler, led, muskler og bindevæv Under kliniske forsøg vedrørende bipolar sygdom:
Musculoskeletal and connective tissue disorders During bipolar disorder clinical trials:
Almene symptomer og reaktioner på administrationsstedet Under kliniske forsøg vedrørende bipolar sygdom:
General disorders and administration site conditions During bipolar disorder clinical trials:
5. 2).
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).
Farmakoterapeutisk klassifikation: andre antiepileptika, ATC- kode:
Pharmacotherapeutic group: other antiepileptics, ATC code:
Resultaterne af farmakodynamiske forsøg tyder på, at lamotrigin er et brugs - og spændingsafhængigt blokerende middel af de spændingsfølsomme natriumkanaler.
The results of pharmacological studies suggest that lamotrigine is a use- and voltage-dependent blocker of voltage gated sodium channels.
Det hæmmer vedvarende, repetitive neuronale fyringer og frigivelse af glutamat (den neurotransmitter, der spiller en nøglerolle i
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).
I undersøgelser, der havde til formål at vurdere lægemidlers effekt på centralnervesystemet, afveg de opnåede resultater ved brug af doser på 240 mg lamotrigin administreret til raske frivillige ikke fra de opnåede resultater ved brug af placebo.
In tests designed to evaluate the central nervous system effects of medicinal products, the results obtained using doses of 240 mg lamotrigine administered to healthy volunteers did not differ from
Derimod hæmmede både 1. 000 mg phenytoin og 10 mg diazepam hver især den finmotoriske, visuelle koordination og øjenbevægelserne signifikant, reducerede balanceevnen og havde en subjektiv sedativ effekt.
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.
Lamotrigin- tabletter med 2 mg er den laveste styrke, som fås, og derfor blev den almindelige doseringsplan i visse tilfælde tilpasset i løbet af titreringsfasen (eksempelvis ved at administrere en tablet med 2 mg hver anden dag, når den beregnede dosis var lavere end 2 mg).
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).
Serumniveauet blev målt i slutningen af uge 2 med titrering, og den efterfølgende dosis blev enten reduceret eller blev ikke øget, hvis koncentrationen oversteg 0, 41 µg/ ml, hvilket er den forventede koncentration hos voksne på dette tidspunkt.
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.
Dosisreduktioner på op til 90% var nødvendige hos nogle patienter i slutningen af uge 2.
Dose reductions of up to 90% were required in some patients at the end of week 2.
38 respondenter (reduktion i frekvensen af anfald på > 40%) blev randomiseret til placebo eller fortsat behandling med lamotrigin.
Thirty-eight responders (> 40% decrease in seizure frequency) were randomised to placebo or continuation of lamotrigine.
Andelen af forsøgspersoner med behandlingssvigt var 84% (16/ 19 forsøgspersoner) i placeboarmen og 58% (11/ 19 forsøgspersoner) i lamotrigin- armen.
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.
Forskellen var ikke statistisk signifikant:
The difference was not statistically significant:
26, 3%, CI 95% - 2, 6% < > 50, 2%, p = 0, 07.
26.3%, CI95% -2.6 %< > 50.2%, p=0.07.
I alt 256 forsøgspersoner i alderen 1 til 24 måneder er blevet eksponeret for lamotrigin i dosisintervallet 1- 15 mg/ kg/ dag i op til 72 uger.
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.
Sikkerhedsprofilen for lamotrigin hos børn i alderen 1 måned til 2 år var omtrent den samme som hos ældre børn, bortset fra at der oftere blev rapporteret om en klinisk signifikant forværring af anfaldene (> = 50%) hos børn under 2 år (26%) sammenlignet med ældre børn (14%).
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%).
Klinisk effekt og sikkerhed ved Lennox- Gastaut- syndrom
Clinical efficacy and safety in Lennox-Gastaut syndrome
Der foreligger ingen data om monoterapi ved anfald, der er forbundet med Lennox- Gastaut- syndrom.
There are no data for monotherapy in seizures associated with Lennox-Gastaut syndrome.
Forsøg SCAB2003 var en randomiseret, dobbeltblindet, placebo - og lithiumkontrolleret multicentervurdering med double dummy og faste doser af langtidsforebyggelsen af recidiv og tilbagefald af depression og/ eller mani hos patienter med bipolar affektiv sindslidelse af type I, der for nylig havde haft eller aktuelt havde en svær depressiv episode.
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.
68 eller placebo i maksimalt 76 uger (18 måneder).
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).
Forsøg SCAB2006 havde samme design som forsøg SCAB2003, men adskilte sig fra forsøg SCAB2003 ved, at der blev vurderet en fleksibel dosis lamotrigin (100 til 400 mg/ dag) og ved, at det omfattede patienter med bipolar affektiv sindslidelse af type I, som for nylig havde haft eller aktuelt havde en manisk episode.
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.
Tabel 7:
67 Table 7:
Resume af resultater fra forsøg, hvor effekten af lamotrigin til forebyggelse af stemningssvingninger hos patienter med bipolar affektiv sindslidelse af type I undersøges
Summary of results from studies investigating the efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder
'Andelen' af patienter, som er hændelsesfri efter 76 uger
‘ Proportion’ of patients being event free at week 76
Forsøg SCAB2003
Study SCAB2003 Bipolar I
Forsøg SCAB2006
Study SCAB2006 Bipolar I
Bipolar affektiv sindslidelse af type I Bipolar affektiv sindslidelse af type I Inklusionskriterium
Inclusion criterion
Svær manisk episode
Major manic episode
Lithium
Lamotrigine Lithium
Placebo Lamotrigin Lithium
Placebo Lamotrigine Lithium
Ingen intervention p- værdi i log rank- test
Intervention free p-value Log rank test
0, 21 0, 006
0.04 -
0, 12 0, 17 0, 24 - 0, 023 0, 006
Depression free
0, 04 -
0.40
Ingen depression p- værdi i log rank- test
p-value Log rank
0, 51 0, 047
0.047
0, 46 0, 209
0.209 -
0, 41 0, 82 0, 71 - 0, 015 0, 167
-value Log rank 0.047 0.209 -
0, 40 -
0.167
Ingen mani p- værdi i log rank- test
Free of mania p-value Log rank test
Endvidere var behandlingsforskellen med hensyn til tiden til maniske/ hypomaniske eller blandede episoder ikke statistisk signifikant.
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.
Forekomsten af selvmordstanker og – handling er blevet evalueret i en poolet analyse af placebo - kontrolleret kliniske forsøg for lamotrigin, hvor 6467 patienter, med forskellige indikationer, er blevet involveret.
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.
I forsøg for bipolar sygdom var mængden af hændelser numerisk, men ikke statistisk signifikant, større for lamotrigin (29/ 1212 [2, 4%]) sammenlignet med placebo (19/ 1054 [1, 8%]).
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%]).
4. 4).
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).
69 Forsøg vedrørende lamotrigins effekt på den kardiale ledning
Study of the effect of lamotrigine on cardiac conduction
Målingerne blev foretaget ved hjælp af EKG i 12 afledninger.
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.
Lamotrigin havde ingen klinisk signifikant effekt på QT- intervallet sammenlignet med placebo.
There was no clinically significant effect of lamotrigine on QT interval compared to placebo.
5. 2 Farmakokinetiske egenskaber
68 5.2 Pharmacokinetic properties
Lamotrigin absorberes hurtigt og fuldstændigt fra tarmen uden signifikant first- pass- metabolisering.
Lamotrigine is rapidly and completely absorbed from the gut with no significant first-pass metabolism.
2, 5 timer efter peroral administration af lamotrigin.
Peak plasma concentrations occur approximately 2.5 hours after oral administration of lamotrigine.
0, 92- 1, 22 l/ kg.
The volume of distribution is 0.92 to 1.22 L/ kg.
Der er dog ingen tegn på, at lamotrigin påvirker farmakokinetikken af andre antiepileptika, og data tyder på, at interaktioner mellem lamotrigin og lægemidler, der metaboliseres af cytokrom P450- enzymer, er usandsynlige.
However, there is no evidence that lamotrigine affects the pharmacokinetics of other AEDs and data suggest that interactions between lamotrigine and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur.
30 ml/ min.
The apparent plasma clearance in healthy subjects is approximately 30 mL/ min.
Mindre end 10% udskilles uændret i urinen.
Less than 10% is excreted unchanged in the urine.
2% af de lamotrigin- relaterede bestanddele udskilles i fæces.
Only about 2% of lamotrigine-related material is excreted in faeces.
33 timer (varierer fra 14 til 103 timer).
The apparent plasma half-life in healthy subjects is estimated to be approximately 33 hours (range 14 to 103 hours).