Lamotrigin Ebb 100 mg Dispergerbar tablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

14-04-2021

Produktens egenskaper Produktens egenskaper (SPC)

12-08-2019

Aktiva substanser:
lamotrigin
Tillgänglig från:
Ebb Medical AB
ATC-kod:
N03AX09
INN (International namn):
lamotrigine
Dos:
100 mg
Läkemedelsform:
Dispergerbar tablett
Sammansättning:
lamotrigin 100 mg Aktiv substans
Receptbelagda typ:
Receptbelagt
Bemyndigande status:
Avregistrerad
Godkännandenummer:
52779
Tillstånd datum:
2016-04-06

Dokument på andra språk

Produktens egenskaper Produktens egenskaper - engelska

14-04-2021

Läs hela dokumentet

Bipacksedel: Information till användaren

Lamotrigin Actavis 2 mg dispergerbara tabletter

Lamotrigin Actavis 5 mg dispergerbara tabletter

Lamotrigin Actavis 25 mg dispergerbara tabletter

Lamotrigin Actavis 50 mg dispergerbara tabletter

Lamotrigin Actavis 100 mg dispergerbara tabletter

Lamotrigin Actavis 200 mg dispergerbara tabletter

lamotrigin

Läs noga igenom denna bipacksedel innan du börjar ta detta läkemedel.

Den innehåller

information som är viktig för dig.

Spara denna bipacksedel, du kan behöva läsa den igen.

Om du har ytterligare frågor vänd dig till läkare eller apotekspersonal.

Detta läkemedel har ordinerats enbart åt dig. Ge det inte till andra. Det kan skada dem,

även om de uppvisar sjukdomstecken som liknar dina.

Om du får biverkningar, tala med läkare eller apotekspersonal. Detta gäller även

eventuella biverkningar som inte nämns i denna information. Se avsnitt 4.

I denna bipacksedel finns information om följande

Vad Lamotrigin Actavis är och vad det används för

Vad du behöver veta innan du

tar Lamotrigin Actavis

Hur du tar Lamotrigin Actavis

Eventuella biverkningar

Hur Lamotrigin Actavis ska förvaras

Förpackningens innehåll och övriga upplysningar

1.

Vad Lamotrigin Actavis är och vad det används för

Lamotrigin Actavis hör till en läkemedelsgrupp som kallas

antiepileptika

. Det används för att

behandla två tillstånd –

epilepsi

bipolär sjukdom.

Lamotrigin Actavis behandlar epilepsi

genom att blockera de signaler i hjärnan som utlöser

epileptiska anfall (attacker).

För vuxna och barn från 13 år och uppåt kan Lamotrigin Actavis användas ensamt eller

tillsammans med andra läkemedel för att behandla epilepsi. Lamotrigin Actavis kan också

användas med andra läkemedel för att behandla de anfall som förekommer vid ett tillstånd

som kallas för Lennox-Gastaut syndrom.

För barn i åldrarna mellan 2 och 12 år kan Lamotrigin Actavis användas tillsammans med

andra mediciner för att behandla dessa tillstånd. Det kan användas som ensam behandling

för att behandla en typ av epilepsi som kallas för typiska absenser.

Lamotrigin Actavis behandlar också bipolär sjukdom.

Personer med bipolär sjukdom (kallas ibland för

manisk depression

) får mycket kraftiga

humörsvängningar med perioder av mani (upphetsning eller lyckorus) omväxlande med

depressionsperioder (djup sorgsenhet eller förtvivlan). För vuxna från 18 år och uppåt kan

Lamotrigin Actavis användas ensamt eller tillsammans med andra läkemedel för att förhindra de

depressionsperioder som förekommer vid bipolär sjukdom. Det är ännu inte känt hur

Lamotrigin Actavis fungerar i hjärnan för att ha denna effekt.

Lamotrigin som finns i Lamotrigin Actavis kan också vara godkänd för att behandla andra

sjukdomar som inte nämns i denna produktinformation. Fråga läkare, apotek eller annan

hälsovårdspersonal om du har ytterligare frågor och följ alltid deras instruktion.

2.

Vad du behöver veta innan du tar Lamotrigin Actavis

Ta inte Lamotrigin Actavis:

om du är allergisk (överkänslig)

mot lamotrigin eller något av övriga innehållsämnen i

Lamotrigin Actavis (anges i avsnitt 6).

Om detta gäller dig:

Tala om det för läkaren

och ta inte Lamotrigin Actavis.

Varningar och försiktighet

Tala med läkare eller apotekspersonal innan du tar Lamotrigin Actavis

om du har några problem med njurarna

om du någon gång har utvecklat hudutslag

efter att du har tagit lamotrigin eller

andra läkemedel mot bipolär sjukdom eller epilepsi, eller om du får hudutslag eller blir

bränd när du tagit lamotrigin och har vistats i solen eller konstgjort ljus (t.ex. solarium).

Läkaren kommer att kontrollera din behandling och rekommenderar dig kanske att

undvika solljus eller att skydda huden mot solstrålarna (t.ex. med solskyddsmedel

och/eller skyddande klädsel).

om du någon gång har utvecklat meningit (hjärnhinneinflammation) efter att du

har tagit lamotrigin (läs beskrivningen av dess symtom under avsnitt 4 i denna

bipacksedel: Sällsynta biverkningar)

om du redan tar medicin som innehåller lamotrigin

om du har ett tillstånd som kallas Brugadas syndrom.

Brugadas syndrom är en

genetisk sjukdom som leder till onormal elektrisk aktivitet i hjärtat. EKG-avvikelser som kan leda

till arytmier (onormal hjärtrytm) kan utlösas av lamotrigin.

Om något av detta gäller dig:

Tala om det för läkaren

som kan bestämma att din dos behöver sänkas eller att

Lamotrigin Actavis inte är lämpligt för dig.

Viktig information om eventuellt livshotande reaktioner

Ett litet antal personer som tar Lamotrigin Actavis får en allergisk reaktion eller hudreaktion som

kan vara livshotande och utvecklas till allvarligare problem om de inte behandlas. Dessa kan

inkludera Stevens-Johnsons syndrom (SJS), toxisk epidermal nekrolys (TEN) samt

läkemedelsreaktion med eosinofili och systemiska symtom (DRESS). Du behöver känna till de

symtom som du ska vara uppmärksam på under tiden du tar Lamotrigin Actavis.

Läs beskrivningen av dessa symtom under avsnitt 4 i denna bipacksedel

under

”Eventuellt livshotande reaktioner: kontakta omedelbart läkare”.

Hemofagocyterande syndrom (HLH)

Rapporter har inkommit om en sällsynt men mycket allvarlig reaktion i immunsystemet hos

patienter som tar lamotrigin.

Kontakta omedelbart läkare eller apotekspersonal

om du får något av följande symptom:

feber, utslag, neurologiska symptom (t.ex. skakningar eller tremor, förvirrat tillstånd,

störningar i hjärnans funktion.

Tankar på att skada dig själv eller på självmord

Läkemedel mot epilepsi används för att behandla olika tillstånd, inklusive epilepsi och bipolär

sjukdom. Personer med bipolär sjukdom kan ibland ha tankar på att skada sig själva eller att begå

självmord. Om du har bipolär sjukdom är det mer troligt att du har sådana tankar:

när du påbörjar behandlingen.

om du tidigare haft tankar på att skada dig själv eller på självmord.

om du är under 25 år.

Om du har oroande tankar eller erfarenheter eller om du märker att du mår sämre eller utvecklar

nya symtom medan du tar Lamotrigin Actavis:

Kontakta läkare snarast eller uppsök närmaste sjukhus för hjälp.

Det kan vara av hjälp att berätta för en familjemedlem, vårdgivare eller nära vän att du

kan bli deprimerad eller få märkbara förändringar i ditt humör, och be dem att läsa denna

bipacksedel. Du kan be dem att tala om för dig om de är oroade kring din depression eller

andra förändringar i ditt beteende.

Ett litet antal personer som behandlas med läkemedel mot epilepsi som t ex Lamotrigin Actavis

har haft tankar på att skada sig själv eller begå självmord. Om du någon gång får dessa tankar,

kontakta omedelbart din läkare

.

Om du tar Lamotrigin Actavis mot epilepsi

Anfall vid vissa typer av epilepsier kan ibland bli värre eller inträffa oftare medan du tar

Lamotrigin Actavis. En del patienter kan uppleva svåra anfall som kan orsaka allvarliga

hälsoproblem. Om dina anfall inträffar oftare eller om du upplever ett svårt anfall när du tar

Lamotrigin Actavis:

Kontakta läkare snarast.

Lamotrigin Actavis ska inte ges till personer under 18 års ålder för behandling av bipolär

sjukdom

. Läkemedel för behandling av depression och andra mentala hälsoproblem ökar risken

för självmordstankar och självmordsbeteende hos barn och ungdomar under 18 år.

Andra läkemedel och Lamotrigin Actavis

Tala om för läkare eller apotekspersonal om du tar, nyligen har tagit eller kan tänkas ta

andra läkemedel

, även receptfria sådana samt naturläkemedel.

Din läkare behöver veta om du tar några andra läkemedel för att behandla epilepsi eller mentala

hälsoproblem. Detta för att säkerställa att du tar rätt dos av Lamotrigin Actavis. Dessa läkemedel

omfattar:

oxkarbazepin, felbamat, gabapentin, levetiracetam, pregabalin, topiramat

eller

zonisamid

som används för att behandla

epilepsi

litium, olanzapin

eller

aripriprazole

som används för att behandla

mentala

hälsoproblem

bupropion

som används för att behandla

mentala hälsoproblem

eller för att

sluta röka

Berätta för din läkare

om du tar något av dessa.

Vissa läkemedel påverkar Lamotrigin Actavis eller gör det mer sannolikt att du får biverkningar.

Dessa omfattar:

valproat

som används för att behandla

epilepsi

mentala hälsoproblem

karbamazepin

som används för att behandla

epilepsi

mentala hälsoproblem

fenytoin, primidon

eller

fenobarbital

som används för att behandla

epilepsi

risperidon

som används för att behandla

mentala hälsoproblem

rifampicin

som är ett

antibiotikum

läkemedel

som används för att behandla

HIV

(en kombination av lopinavir och ritonavir

eller atazanavir och ritonavir

hormonella preventivmedel

som till exempel

p-piller (se nedan)

Berätta för din läkare

om du tar eller om du börjar eller slutar ta något av dessa.

Hormonella preventivmedel (till exempel p-piller) kan påverka det sätt på vilket

Lamotrigin Actavis fungerar

Läkaren kan rekommendera att du använder en speciell typ av hormonellt preventivmedel eller en

annan preventivmetod som till exempel kondom, pessar eller spiral. Om du använder ett

hormonellt preventivmedel som p-piller kan läkaren eventuellt ta blodprov för att kontrollera

Lamotrigin Actavis-nivån. Om du planerar att börja använda hormonellt preventivmedel:

Berätta det för din läkare

som diskuterar lämpliga preventivmetoder med dig.

Lamotrigin Actavis kan också påverka det sätt som hormonella preventivmedel fungerar på, även

om det är osannolikt att de blir mindre effektiva. Om du använder ett hormonellt preventivmedel

och märker någon förändring i din menscykel som till exempel en mensliknande blödning eller

småblödningar mellan menstruationerna:

Berätta det för din läkare

. Det kan vara tecken på att Lamotrigin Actavis påverkar det sätt

som ditt preventivmedel fungerar på.

Graviditet och amning

Om du är gravid eller ammar, tror att du kan vara gravid eller planerar att skaffa

barn, rådfråga läkare eller apotekspersonal innan du använder detta läkemedel.

Du ska inte upphöra med behandlingen mot din epilepsi när du är gravid

utan

att diskutera det med din läkare

. Det är speciellt viktigt om du har epilepsi.

Graviditeten kan ändra effektiviteten av Lamotrigin Actavis, varför läkaren kan ta

blodprover för att kontrollera Lamotrigin Actavis-nivån så att dosen eventuellt kan

ändras.

Det kan finnas en liten ökad risk för missbildning hos foster, inklusive läpp- eller

gomspalt, om Lamotrigin Actavis tas under de första tre månaderna av graviditeten.

Läkaren kan också ge dig rådet att ta extra

folsyra

om du planerar att bli gravid och

under tiden du är gravid.

Om du ammar eller planerar att amma, rådfråga läkare eller apotekspersonal innan

du använder detta läkemedel

. Den aktiva substansen i Lamotrigin Actavis går över till

bröstmjölk och kan påverka ditt barn. Din läkare kommer att diskutera risker och fördelar

med amning under behandling med Lamotrigin Actavis. Om du väljer att amma kommer

läkaren att kontrollera barnet då och då för att se om barnet uppvisar dåsighet, utslag eller

dålig viktuppgång. Informera läkaren om du upptäcker något av dessa symtom hos ditt barn.

Körförmåga och användning av maskiner

Lamotrigin Actavis kan orsaka yrsel och dubbelseende.

Kör inte något fordon eller använd maskiner om du inte känner dig bra.

Om du har epilepsi ska du tala med din läkare om att köra fordon och använda maskiner.

Du är själv ansvarig för att bedöma om du är i kondition att framföra motorfordon eller utföra

arbete som kräver skärpt vaksamhet. En av faktorerna som kan påverka din förmåga i dessa

avseenden är användning av läkemedel på grund av deras effekter och/eller biverkningar.

Beskrivning av dessa effekter och biverkningar finns i andra avsnitt. Läs därför all information i

denna bipacksedel för vägledning. Diskutera med din läkare eller apotekspersonal om du är

osäker.

Lamotrigin Actavis innehåller natrium

Detta läkemedel innehåller mindre än 1 mmol natrium (23 mg) per dos, dvs. är näst intill

natriumfritt.

Lamotrigin Actavis innehåller sulfiter (E220-E228)

Kan i sällsynta fall ge allvarliga överkänslighetsreaktioner och kramp i luftrören.

3.

Hur du tar Lamotrigin Actavis

Ta alltid detta läkemedel enligt läkarens eller apotekspersonalens anvisningar

Rådfråga läkare eller apotekspersonal om du är osäker.

Hur mycket Lamotrigin Actavis du ska ta

Det kan ta ett tag att finna den Lamotrigin Actavis-dos som är bäst för dig. Dosen du tar beror på:

din ålder

om du tar Lamotrigin Actavis tillsammans med andra läkemedel eller inte

om du har problem med njurarna eller levern.

Din läkare börjar med att ge dig en låg dos och ökar dosen gradvis under några veckor tills du når

en dos som fungerar för dig (kallas den effektiva dosen).

Ta aldrig mer Lamotrigin Actavis än

din läkare har sagt.

Den vanliga effektiva dosen Lamotrigin Actavis för vuxna och barn från 13 års ålder är mellan

100 mg och 400 mg dagligen.

För barn mellan 2 och 12 års ålder beror den effektiva dosen på kroppsvikten – vanligtvis är den

mellan 1 mg och 15 mg för varje kilogram av barnets vikt upp till en underhållsdos på högst 200

mg dagligen.

Lamotrigin Actavis rekommenderas inte för barn under 2 år.

Hur du tar din dos Lamotrigin Actavis

Ta din dos Lamotrigin Actavis en eller två gånger dagligen enligt läkarens anvisningar. Du kan ta

den med eller utan mat.

Din läkare kan också tala om för dig att du ska börja eller sluta ta andra läkemedel, beroende på

vilket tillstånd du behandlas för och hur du reagerar på behandlingen.

Ta alltid hela den dos

som läkaren har ordinerat. Ta aldrig bara en del av en tablett.

Lamotrigin Actavis dispergerbara tabletter kan antingen sväljas hela med lite vatten, tuggas, eller

blandas med vatten till en flytande medicin.

Om du tuggar tabletten

Du behöver kanske dricka lite vatten samtidigt så att tabletten löses upp i munnen. Drick sedan

lite mer vatten så att du säkert sväljer all medicin.

Så här gör du en flytande medicin

Lägg tabletten i ett glas med minst så mycket vatten att hela tabletten täcks.

Rör om så att tabletten löses upp eller vänta tills tabletten är helt upplöst.

Drick all vätskan.

Tillsätt lite mer vatten i glaset och drick det för att säkerställa att inget läkemedel är kvar i

glaset.

Om du har tagit för stor mängd av Lamotrigin Actavis

Om du har tagit för stor mängd av Lamotrigin Actavis eller ett barn fått i sig läkemedlet av

misstag:

Kontakta läkare, sjukhuspersonal, apotekspersonal eller Giftinformationscentralen

(tel. 112) omedelbart för bedömning av risken samt rådgivning

Visa dem Lamotrigin

Actavis-förpackningen om möjligt.

Om du tar för mycket Lamotrigin Actavis

är risken större att du får allvarliga biverkningar

vilka kan vara livshotande.

En person som tagit för mycket Lamotrigin Actavis kan få något av dessa symtom:

snabba, okontrollerade ögonrörelser

(nystagmus)

klumpighet och bristande koordinationsförmåga som påverkar balansen

(ataxi)

förändringar i hjärtrytmen (upptäcks vanligen på EKG)

förlust av medvetandet, krampanfall (konvulsioner) eller koma.

Om du har glömt att ta en dos Lamotrigin Actavis

Ta inte extra tabletter eller dubbel dos för att kompensera för en glömd dos

Ta bara

din nästa dos vid den vanliga tiden.

Om du har glömt att ta flera doser av Lamotrigin Actavis

Fråga din läkare hur du ska börja ta medicinen igen.

Det är viktigt att du frågar om detta.

Sluta inte ta Lamotrigin Actavis utan att ha rådgjort med läkare

Ta Lamotrigin Actavis så länge din läkare rekommenderar det. Sluta inte utan att läkaren talar om

för dig att du ska göra det.

Om du tar Lamotrigin Actavis för epilepsi

För att sluta ta Lamotrigin Actavis

är det viktigt att du minskar dosen gradvis

under omkring

2 veckor. Om du plötsligt slutar att ta Lamotrigin Actavis kan din epilepsi komma tillbaka eller

förvärras.

Om du tar Lamotrigin Actavis mot bipolär sjukdom

Det kan ta tid innan Lamotrigin Actavis verkar och därför kommer du troligtvis inte att må bättre

på en gång. Om du slutar ta Lamotrigin Actavis behöver dosen inte minskas gradvis. Men du bör

ändå prata med din läkare först, om du vill sluta ta Lamotrigin Actavis.

4.

Eventuella biverkningar

Liksom alla läkemedel kan detta läkemedel orsaka biverkningar men alla användare behöver inte

få dem.

Eventuellt livshotande reaktioner: kontakta omedelbart läkare

Ett litet antal personer som tar Lamotrigin Actavis kan få en allergisk reaktion eller hudreaktion

som kan vara livshotande och utvecklas till allvarligare problem om de inte behandlas.

Det är troligare att dessa symtom uppträder under de första månaderna av behandling med

Lamotrigin Actavis, särskilt om startdosen är för hög eller om dosen ökas för snabbt, eller om

Lamotrigin Actavis tas med ett annat läkemedel som heter

valproat

. Vissa av dessa symtom är

vanligare hos barn, så föräldrar ska vara extra uppmärksamma.

Symtom på sådana reaktioner är bland annat:

hudutslag eller rodnad,

vilket kan utvecklas till livshotande hudreaktioner som inkluderar

utbrett hudutslag med blåsor och flagnande hud, framför allt runt munnen, näsan, ögonen

och könsorganen (

Stevens-Johnsons syndrom

), omfattande flagning av huden (mer än 30 %

av kroppsytan -

toxisk epidermal nekrolys

) eller omfattande hudutslag med påverkan på

lever, blodet och andra kroppsorgan (läkemedelsreaktion med eosinofili och systemiska

symtom, som också kallas för DRESS överkänslighetssyndrom)

sår i munnen, halsen, näsan eller underlivet

ont i munnen eller röda svullna ögon (konjunktivit)

feber

, influensaliknande symtom eller sömnighet

svullnad runt ansiktet

eller

svullna körtlar

i hals, armhåla eller ljumske

oväntad blödning eller blåmärke

eller att fingrarna blir blå

ont i halsen

eller fler infektioner (till exempel förkylningar) än vanligt

ökade nivåer av leverenzymer

sett i blodprover

en ökning av en typ av vita blodkroppar

(eosinofiler)

förstorade lymfkörtlar

påverkan på organ i kroppen inklusive lever och njurar

I många fall är dessa symtom tecken på mindre allvarliga biverkningar.

Men du måste vara

medveten om att de kan vara livshotande och kan utvecklas till mer allvarliga problem

såsom organsvikt, om de inte behandlas.

Om du upptäcker något av dessa symtom:

Kontakta läkare omedelbart.

Din läkare kan bestämma att prover ska tas på din lever, dina

njurar eller ditt blod och kan säga att du ska sluta ta Lamotrigin Actavis.

Om du har

utvecklat Stevens-Johnsons syndrom eller toxisk epidermal nekrolys kommer din läkare att

säga till dig att du aldrig får använda lamotrigin igen.

Hemofagocyterande syndrom (HLH)

(se avsnitt 2: Vad du behöver veta innan du tar

Lamotrigin Actavis)

Mycket vanliga biverkningar

Kan förekomma hos

fler än 1 av 10

användare:

huvudvärk

hudutslag

Vanliga biverkningar

Kan förekomma hos

upp till 1 av 10

användare:

aggressivitet eller irritabilitet

sömnighet eller dåsighet

yrsel

skakningar eller tremor

sömnsvårigheter

(insomnia)

upprördhetskänslor

diarré

torr mun

illamående, kräkning

trötthet

värk i rygg eller leder eller någon annanstans

Mindre vanliga biverkningar

Kan förekomma hos

upp till 1 av 100

användare:

klumpighet och bristande koordinationsförmåga (

ataxi

dubbelseende eller dimsyn

onormalt håravfall eller förtunning

(alopeci)

hudutslag eller solskador efter exponering för sol eller konstgjort ljus (fotosensitivitet)

Sällsynta biverkningar

Kan förekomma hos

upp till 1 av 1 000

användare:

en livshotande hudreaktion

(Stevens-Johnsons syndrom): (se även information i början av

avsnitt 4)

en grupp av symtom som inkluderar: feber, illamående, kräkning, huvudvärk, nackstelhet

och extrem känslighet för starkt ljus. Detta kan bero på en inflammation i membranen som

skyddar hjärnan och ryggraden

(meningit).

Dessa symtom försvinner vanligen när

behandlingen avbryts.

Kontakta din läkare

om symtomen fortsätter eller blir värre.

snabba, okontrollerade ögonrörelser

(nystagmus

klåda i ögonen med utsöndringar och skorpor på ögonlocken

(konjunktivit)

Mycket sällsynta biverkningar

Kan förekomma hos

upp till 1 av 10 000

användare:

en livshotande hudreaktion

(toxisk epidermal nekrolys), (se även informationen i början av

avsnitt 4)

läkemedelsreaktion med eosinofili och systemiska symtom (DRESS), (

se även

informationen i början av avsnitt 4)

förhöjd temperatur

(feber), (se även informationen i början av avsnitt 4)

svullnad runt ansiktet (

ödem

) eller svullna körtlar i hals, armhåla eller

ljumske (

lymfadenopati

, (se även informationen i början av avsnitt 4)

förändringar i leverfunktionen, vilket visar sig i blodprover, eller leversvikt, (

se även

informationen i början av avsnitt 4)

en allvarlig störning i blodkoaguleringen som kan orsaka oväntad blödning eller

blåmärke

(disseminerad intravaskulär koagulation),

se även informationen i början av

avsnitt 4)

förändringar som kan visa sig i blodprover – bland annat minskat antal röda

blodkroppar

(anemi)

, minskat antal vita blodkroppar

(leukopeni, neutropeni,

agranulocytos)

, minskat antal blodplättar

(trombocytopeni)

, minskat antal av alla dessa

blodkroppstyper

(pancytopeni)

och en sjukdom i benmärgen som kallas

aplastisk anemi

hallucinationer (att ”se” eller ”höra” saker som egentligen inte finns)

förvirring

känsla av att ”vingla” eller vara ostadig när du rör dig

okontrollerbara kroppsrörelser

(tics)

, okontrollerbara muskelspasmer som påverkar ögonen,

huvudet och bålen

(koreoatetos)

eller andra ovanliga kroppsrörelser som ryckningar,

skakningar eller stelhet

oftare förekommande anfall hos dem som redan har epilepsi

förvärrade symtom hos dem som redan har Parkinsons sjukdom

lupusliknande reaktion (symtomen kan inkludera: rygg- eller ledsmärta som ibland kan

åtföljas av feber och/eller allmän ohälsa

Hemofagocyterande syndrom (HLH) (se avsnitt 2: Vad du behöver veta innan du tar

Lamotrigin Actavis).

Andra biverkningar

Andra biverkningar har observerats hos ett mindre antal människor men den exakta frekvensen är

okänd:

Det har förkommit rapporter om skelettpåverkan inklusive osteopeni och osteoporos

(förtunnung av skelettbenet) och benbrott. Kontrollera med läkare eller apotekspersonal om

du står på antiepileptisk långtidsbehandling, har en historia av osteoporos eller tar

steroider.

mardrömmar

sämre immunförsvar till följd av lägre nivåer av immunoglobuliner, en sorts blodkroppar

som hjälper till att skydda mot infektioner.

Rapportering av biverkningar

Om du får biverkningar, tala med läkare apotekspersonal eller sjuksköterska. Detta gäller även

biverkningar som inte nämns i denna information. Du kan också rapportera biverkningar direkt

via:

Läkemedelsverket

Box 26

751 03 Uppsala

www.lakemedelsverket.se

Genom att rapportera biverkningar kan du bidra till att öka informationen om läkemedels

säkerhet.

5.

Hur Lamotrigin Actavis ska förvaras

Förvaras utom syn- och räckhåll för barn.

2 mg (blister): Förvaras vid högst 30 °C.

Tablettburk: Inga särskilda förvaringsanvisningar.

5 mg: Förvaras vid högst 30 °C.

25 mg, 50 mg, 100 mg och 200 mg (blister): Inga särskilda förvaringsanvisningar.

Används före utgångsdatum som anges på blister, kartong eller burk efter EXP. Utgångsdatumet

är den sista dagen i angiven månad.

Medicinen ska inte kastas i avloppet eller bland hushållsavfall. Fråga apotekspersonalen hur man

gör med mediciner som inte längre används. Dessa åtgärder är till för att skydda miljön.

6.

Förpackningens innehåll och övriga upplysningar

Innehållsdeklaration

Den aktiva substansen är lamotrigin. Varje Lamotrigin Actavis dispergerbar tablett innehåller

2 mg, 5 mg, 25 mg, 50 mg, 100 mg eller 200 mg lamotrigin.

Övriga innehållsämnen är: tungt magnesiumsubkarbonat, mikrokristallin cellulosa, povidon,

hydroxipropylcellulosa, sackarinnatrium, krospovidon, magnesiumstearat, guargummi och

svartvinbärsarom (innehållande maltodextrin, akaciagummi, triacetin, mjölksyra, maltol,

etylalkohol, ättiksyra, propylenglykol och sulfiter).

Läkemedlets utseende och förpackningsstorlekar

Lamotrigin Actavis 2 mg dispergerbar tablett: vit eller nästan vit, rund, märkt ”2” på ena sidan.

Storlek: diameter 6 mm.

Lamotrigin Actavis 5 mg dispergerbar tablett: vit eller nästan vit, kapselformad, bikonvex, märkt

”5” på ena sidan. Storleken: diameter 5,5 x 11 mm.

Lamotrigin Actavis 25 mg, 50 mg, 100 mg och 200 mg dispergerbar tablett: vit eller nästan vit,

rund, platt, märkt ”25”, ”50”, ”100” eller ”200” på den ena sidan. Storlek: diameter 5,5, 7,9 eller

11,5 mm.

Blisterförpackningar (Al/PVC): 7, 10, 20, 21, 28, 30, 40, 42, 50, 50x1, 56, 60, 98, 98x1, 100,

100x1 och 200 dispergerbara tabletter

2 mg burk (PP): 30 och 100 dispergerbara tabletter

Eventuellt kommer inte alla förpackningsstorlekar att marknadsföras.

Innehavare av godkännande för försäljning och tillverkare

Innehavare av godkännande för försäljning

Actavis Group PTC ehf.

Reykjavíkurvegi 76-78

220 Hafnarfjördur

Island

Tillverkare

Actavis Group PTC ehf.

Reykjavíkurvegur 76-78

220 Hafnarfjördur

Island

eller

Specifar S.A

1, 28 Octovriou str.

123 51 Ag. Varvara

Aten

Grekland

Lokal företrädare

Teva Sweden AB

Box 1070

251 10 Helsingborg

Denna bipacksedel ändrades senast

2021-04-13

Läs hela dokumentet

SUMMARY OF PRODUCT CHARACTERISTICS

NAME OF THE MEDICINAL PRODUCT

Lamotrigin Actavis 2 mg dispersible tablets.

Lamotrigin Actavis 5 mg dispersible tablets.

Lamotrigin Actavis 25 mg dispersible tablets.

Lamotrigin Actavis 50 mg dispersible tablets.

Lamotrigin Actavis 100 mg dispersible tablets.

Lamotrigin Actavis 200 mg dispersible tablets.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each /.../ 2 mg dispersible tablet contains 2 mg lamotrigine.

Each /.../ 5 mg dispersible tablet contains 5 mg lamotrigine.

Each /…/ 25 mg dispersible tablet contains 25 mg lamotrigine.

Each /…/ 50 mg dispersible ablet contains 50 mg lamotrigine.

Each /…/ 100 mg dispersible tablet contains 100 mg lamotrigine.

Each /…/ 200 mg dispersible tablet contains 200 mg lamotrigine.

Excipient(s) with known effect:

Each dispersable tablet contains less than 0,001 % sulphites (E220-E228) in the flavour component.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Dispersible tablet.

2 mg dispersible tablets:

White or almost white, round, flat, marked “2” on one side and have a diameter of 6 mm.

5 mg dispersible tablets:

White or almost white, capsule shaped, biconvex, marked “5” on one side. The size is 5.5 x 11 mm.

25 mg dispersible tablets:

White or almost white, round, flat, marked “25” on one side and have a diameter of 5.5 mm.

50 mg dispersible tablets:

White or almost white, round, flat, marked “50” on one side and have a diameter of 7 mm.

100 mg dispersible tablets:

White or almost white, round, flat, marked “100” on one side and have a diameter of 9 mm.

200 mg dispersible tablets:

White or almost white, round, flat, marked “200” on one side and have a diameter of 11.5 mm.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Epilepsy

Adults and adolescents aged 13 years and above

- Adjunctive or monotherapy treatment of partial seizures and generalised seizures, including

tonic-clonic seizures.

- Seizures associated with Lennox-Gastaut syndrome. /…/ is given as adjunctive therapy but

may be the initial antiepileptic drug (AED) to start with in Lennox-Gastaut syndrome.

Children and adolescents aged 2 to 12 years

- Adjunctive treatment of partial seizures and generalised seizures, including tonic-clonic

seizures and the seizures associated with Lennox-Gastaut syndrome.

- Monotherapy of typical absence seizures.

Bipolar disorder

Adults aged 18 years and above

Prevention

depressive

episodes

patients

with

bipolar

disorder

experience

predominantly depressive episodes (see section 5.1).

/…/ is not indicated for the acute treatment of manic or depressive episodes.

4.2

Posology and method of administration

Posology

If the calculated dose of lamotrigine (for example for treatment of children with epilepsy or patients

with hepatic impairment) does not equate to whole tablets, the dose to be administered is that equal to

the lower number of whole tablets.

Restarting therapy

Prescribers should assess the need for escalation to maintenance dose when restarting /…/ in patients

who have discontinued /…/ for any reason, since the risk of serious rash is associated with high initial

doses and exceeding the recommended dose escalation for lamotrigine (see section 4.4). The greater

the interval of time since the previous dose, the more consideration should be given to escalation to the

maintenance dose. When the interval since discontinuing lamotrigine exceeds five half-lives (see

section 5.2), /…/ should generally be escalated to the maintenance dose according to the appropriate

schedule.

It is recommended that /…/ not be restarted in patients who have discontinued due to rash associated

with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.

Epilepsy

The recommended dose escalation and maintenance doses for adults and adolescents aged 13 years

and above (Table 1) and for children and adolescents aged 2 to 12 years (Table 2) are given below.

Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see

section 4.4).

When concomitant AEDs are withdrawn or other AEDs/medicinal products are added on to treatment

regimes containing lamotrigine, consideration should be given to the effect this may have on

lamotrigine pharmacokinetics (see section 4.5).

Table 1: Adults and adolescents aged 13 years and above – recommended treatment regimen in

epilepsy

Treatment regimen

Weeks 1 + 2

Weeks 3 + 4

Usual maintenance dose

Monotherapy:

25 mg/day

(once a day)

50 mg/day

(once a day)

100 − 200 mg/day

(once a day or two divided doses)

achieve

maintenance,

doses

increased

maximum

50 - 100 mg

every

two weeks

until

optimal

response is achieved

500 mg/day

been

required

some

patients to achieve desired response

Adjunctive therapy WITH valproate

(inhibitor of lamotrigine glucuronidation – see section 4.5)

:

This dosage regimen should

used

with

valproate

regardless

concomitant

medicinal

products

12.5 mg/day

(given as 25 mg

alternate

days)

25 mg/day

(once a day)

100 − 200 mg/day

(once a day or two divided doses)

achieve

maintenance,

doses

increased by maximum of 25 - 50 mg every

one to two weeks until optimal response is

achieved

Adjunctive

therapy

WITHOUT

valproate

and

WITH

inducers

of

lamotrigine

glucuronidation

(see

section 4.5)

:

This dosage regimen should

be used without valproate

but with:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

50 mg/day

(once a day)

100 mg/day

(two

divided

doses)

200 − 400 mg/day

(two divided doses)

achieve

maintenance,

doses

increased by maximum of 100 mg every

one to two weeks until optimal response is

achieved

700 mg/day

been

required

some

patients to achieve desired response

Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation

(see section 4.5)

:

This dosage regimen should

used

with

other

medicinal products that do

not significantly inhibit or

induce

lamotrigine

glucuronidation

25 mg/day

(once a day)

50 mg/day

(once a day)

100 − 200 mg/day

(once a day or two divided doses)

achieve

maintenance,

doses

increased

maximum

50 - 100 mg

every

weeks

until

optimal

response is achieved

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not

known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate

should be used.

Table 2: Children and adolescents aged 2 to 12 years - recommended treatment regimen in epilepsy

(total daily dose in mg/kg body weight/day)

Treatment regimen

Weeks 1 + 2

Weeks 3 + 4

Usual maintenance dose

Monotherapy

of

typical

absence seizures:

0.3 mg/kg/day

(once

divided

doses)

0.6 mg/kg/day

(once a day or

divided

doses)

1 – 15 mg/kg/day

(once a day or two divided doses)

To achieve maintenance, doses may be

increased

maximum

0.6 mg/kg/day every one to two weeks

until optimal response is achieved, with

maximum

maintenance

dose

200 mg/day

Adjunctive therapy WITH valproate

(inhibitor of lamotrigine glucuronidation – see section 4.5)

:

This dosage regimen should

used

with

valproate

regardless

other

concomitant

medicinal

products

0.15 mg/kg/day*

(once a day)

0.3 mg/kg/day

(once a day)

1 − 5 mg/kg/day

(once a day or two divided doses)

To achieve maintenance, doses may be

increased

maximum

0.3 mg/kg/day every one to two weeks

until optimal response is achieved, with

maximum

maintenance

dose

200 mg/day

Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation

(see

section 4.5)

:

This dosage regimen should

be used without valproate

but with:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

0.6 mg/kg/day

(two

divided

doses)

1.2 mg/kg/day

(two

divided

doses)

5 − 15 mg/kg/day

(once a day or two divided doses)

To achieve maintenance, doses may be

increased

maximum

1.2 mg/kg/day every one to two weeks

until optimal response is achieved, with

maximum

maintenance

dose

400 mg/day

Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation

(see section 4.5)

:

This dosage regimen should

used

with

other

medicinal products that do

not significantly inhibit or

induce

lamotrigine

glucuronidation

0.3 mg/kg/day

(once

divided

doses)

0.6 mg/kg/day

(once a day or

divided

doses)

1 − 10 mg/kg/day

(once a day or two divided doses)

To achieve maintenance, doses may be

increased

maximum

0.6 mg/kg/day every one to two weeks

until optimal response is achieved, with

maximum

maintenance

dose

200 mg/day

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently

not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent

valproate should be used.

* If the calculated daily dose in patients taking valproate is 1 mg or more but less than 2 mg, then /…/ 2 mg

dispersible tablets may be taken on alternate days for the first two weeks. If the calculated daily dose in

patients taking valproate is less than 1 mg, then /…/ should not be administered.

To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose

reviewed as weight changes occur. It is likely that patients aged two to six years will require a

maintenance dose at the higher end of the recommended range.

If epileptic control is achieved with adjunctive treatment, concomitant AEDs may be withdrawn and

patients continued on /…/ monotherapy.

Children below 2 years

There are limited data on the efficacy and safety of lamotrigine for adjunctive therapy of partial

seizures in children aged 1 month to 2 years (see section 4.4). There are no data in children below 1

month of age. Thus /…/ is not recommended for use in children below 2 years of age. If, based on

clinical need, a decision to treat is nevertheless taken, see sections 4.4, 5.1 and 5.2.

Bipolar disorder

The recommended dose escalation and maintenance doses for adults of 18 years of age and above are

given in the tables below. The transition regimen involves escalating the dose of lamotrigine to a

maintenance stabilisation dose over six weeks (Table 3) after which other psychotropic medicinal

products and/or AEDs can be withdrawn, if clinically indicated (Table 4). The dose adjustments

following addition of other psychotropic medicinal products and/or AEDs are also provided below

(Table 5). Because of the risk of rash the initial dose and subsequent dose escalation should not be

exceeded (see section 4.4).

Table 3: Adults aged 18 years and above - recommended dose escalation to the maintenance total

daily stabilisation dose in treatment of bipolar disorder

Treatment Regimen

Weeks 1 + 2

Weeks 3 + 4

Week 5

Target

Stabilisation Dose

(Week 6)*

Monotherapy with lamotrigine OR adjunctive therapy WITHOUT valproate and WITHOUT

inducers of lamotrigine glucuronidation

(see section 4.5):

This dosage regimen should be

used with other medicinal products

that do not significantly inhibit or

induce lamotrigine glucuronidation

25 mg/day

(once a day)

50 mg/day

(once a day

or two

divided

doses)

mg/day

(once a

day or two

divided

doses)

200 mg/day –

usual target dose

for optimal

response (once a

day or two

divided doses)

Doses in the range

100 – 400 mg/day

used in clinical

trials

Adjunctive therapy WITH valproate

(inhibitor of lamotrigine glucuronidation – see section 4.5):

This dosage regimen should be

used with valproate regardless of

any concomitant medicinal

products

12.5 mg/day

(given as 25

mg on

alternate

days)

25 mg/day

(once a day)

50 mg/day

(once a

day or two

divided

doses)

100 mg/day –

usual target dose

for optimal

response (once a

day or two

divided doses)

Maximum dose of

200 mg/day can

be used depending

on clinical

response

Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation

(see section 4.5):

This dosage regimen should be

used without valproate but with:

50 mg/day

(once a day)

100 mg/day

(two divided

mg/day

300 mg/day in

week 6, if

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

doses)

(two

divided

doses)

necessary

increasing to

usual target dose

of 400 mg/day in

week 7, to achieve

optimal response

(two divided

doses)

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is

currently not known (see section 4.5), the dose escalation as recommended for lamotrigine with

concurrent valproate, should be used.

* The Target stabilisation dose will alter depending on clinical response

Table 4: Adults aged 18 years and above - maintenance stabilisation total daily dose

following withdrawal of concomitant medicinal products in treatment of bipolar disorder

Once the target daily maintenance stabilisation dose has been achieved, other medicinal products may

be withdrawn as shown below.

Treatment Regimen

Current

lamotrigine

stabilisation

dose (prior to

withdrawal)

Week 1

(beginning

with

withdrawal)

Week 2

Week 3 onwards *

Withdrawal of valproate

(inhibitor of lamotrigine glucuronidation – see section 4.5), depending on

original dose of lamotrigine:

100 mg/day

200 mg/day

Maintain this dose (200 mg/day)

(two divided doses)

When valproate is

withdrawn, double the

stabilisation dose, not

exceeding an increase of

more than 100 mg/week

200 mg/day

300 mg/day

400 mg/day

Maintain this dose

(400 mg/day)

Withdrawal of inducers of lamotrigine glucuronidation

(see section 4.5), depending on original

dose of lamotrigine:

400 mg/day

400 mg/day

300 mg/day

200 mg/day

300 mg/day

300 mg/day

225 mg/day

150 mg/day

This dosage regimen should

be used when the following

are withdrawn:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

200 mg/day

200 mg/day

150 mg/day

100 mg/day

Withdrawal of medicinal products that do NOT significantly inhibit or induce lamotrigine

glucuronidation

(see section 4.5):

This dosage regimen should

be used when other

medicinal products that do

not significantly inhibit or

induce lamotrigine

glucuronidation are

withdrawn

Maintain target dose achieved in dose escalation (200 mg/day; two

divided doses)

(dose range 100 – 400 mg/day)

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is

currently not known (see section 4.5), the treatment regimen recommended for lamotrigine is to

initially maintain the current dose and adjust the lamotrigine treatment based on clinical response.

* Dose may be increased to 400 mg/day as needed

Table 5: Adults aged 18 years and above - adjustment of lamotrigine daily dosing following

the addition of other medicinal products in treatment of bipolar disorder

There is no clinical experience in adjusting the lamotrigine daily dose following the addition of

other medicinal products. However, based on interaction studies with other medicinal products,

the following recommendations can be made

Treatment Regimen

Current

lamotrigine

stabilisation

dose (prior to

addition)

Week 1

(beginning

with addition)

Week 2

Week 3 onwards

Addition of valproate

(inhibitor of lamotrigine glucuronidation – see section 4.5), depending on

original dose of lamotrigine:

200 mg/day

100 mg/day

Maintain this dose (100 mg/day)

300 mg/day

150 mg/day

Maintain this dose (150 mg/day)

This dosage regimen should

be used when valproate is

added regardless of any

concomitant medicinal

products

400 mg/day

200 mg/day

Maintain this dose (200 mg/day)

Addition of inducers of lamotrigine glucuronidation in patients NOT taking valproate

(see

section 4.5), depending on original dose of lamotrigine:

200 mg/day

200 mg/day

300 mg/day

400 mg/day

150 mg/day

150 mg/day

225 mg/day

300 mg/day

This dosage regimen should

be used when the following

are added without valproate:

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

100 mg/day

100 mg/day

150 mg/day

200 mg/day

Addition of medicinal products that do NOT significantly inhibit or induce lamotrigine

glucuronidation

(see section 4.5):

This dosage regimen should

be used when other

medicinal products that do

not significantly inhibit or

induce lamotrigine

glucuronidation are added.

Maintain target dose achieved in dose escalation (200 mg/day; dose

range 100 – 400 mg/day)

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is

currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with

concurrent valproate, should be used.

Discontinuation of /…/ in patients with bipolar disorder

In clinical trials, there was no increase in the incidence, severity or type of adverse reactions following

abrupt termination of lamotrigine versus placebo. Therefore, patients may terminate /…/ without a

step-wise reduction of dose.

Children and adolescents below 18 years

/…/ is not recommended for use in children below 18 years of age because a randomised withdrawal

study demonstrated no significant efficacy and showed increased reporting of suicidality (see section

4.4 and 5.1).

General dosing recommendations for /…/ in special patient populations

Women taking hormonal contraceptives

The use of an ethinyloestradiol/levonorgestrel (30 μg/150 μg) combination increases the clearance of

lamotrigine by approximately two-fold, resulting in decreased lamotrigine levels. Following titration,

higher maintenance doses of lamotrigine (by as much as two-fold) may be needed to attain a maximal

therapeutic response. During the pill-free week, a two-fold increase in lamotrigine levels has been

observed. Dose-related adverse events cannot be excluded. Therefore, consideration should be given

to using contraception without a pill-free week, as first-line therapy (for example, continuous

hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).

Starting hormonal contraceptives in patients already taking maintenance doses of lamotrigine and

NOT taking inducers of lamotrigine glucuronidation

The maintenance dose of lamotrigine will in most cases need to be increased by as much as two-fold

(see sections 4.4 and 4.5). It is recommended that from the time that the hormonal contraceptive is

started, the lamotrigine dose is increased by 50 to 100 mg/day every week, according to the individual

clinical response. Dose increases should not exceed this rate, unless the clinical response supports

larger increases. Measurement of serum lamotrigine concentrations before and after starting hormonal

contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is

being maintained. If necessary, the dose should be adapted. In women taking a hormonal contraceptive

that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring

should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle.

Therefore, consideration should be given to using contraception without a pill-free week, as first-line

therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4

and 4.5).

Stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and

NOT taking inducers of lamotrigine glucuronidation

The maintenance dose of lamotrigine will in most cases need to be decreased by as much as 50% (see

sections 4.4 and 4.5). It is recommended to gradually decrease the daily dose of lamotrigine by 50-100

mg each week (at a rate not exceeding 25% of the total daily dose per week) over a period of 3 weeks,

unless the clinical response indicates otherwise. Measurement of serum lamotrigine concentrations

before and after stopping hormonal contraceptives may be considered, as confirmation that the

baseline concentration of lamotrigine is being maintained. In women who wish to stop taking a

hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum

lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to

21 of the pill cycle. Samples for assessment of lamotrigine levels after permanently stopping the

contraceptive pill should not be collected during the first week after stopping the pill.

Starting lamotrigine in patients already taking hormonal contraceptives

Dose escalation should follow the normal dose recommendation described in the tables.

Starting and stopping hormonal contraceptives in patients already taking maintenance doses of

lamotrigine and TAKING inducers of lamotrigine glucuronidation

Adjustment to the recommended maintenance dose of lamotrigine may not be required.

Use with atazanavir/ritonavir

No adjustments to the recommended dose escalation of lamotrigine should be necessary when

lamotrigine is added to the existing atazanavir/ritonavir therapy.

In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers,

the lamotrigine dose may need to be increased if atazanavir/ritonavir is added, or decreased if

atazanavir/ritonavir is discontinued. Plasma lamotrigine monitoring should be conducted before and

during 2 weeks after starting or stopping atazanavir/ritonavir, in order to see if lamotrigine dose

adjustment is needed (see section 4.5).

Use with lopinavir/ritonavir

No adjustments to the recommended dose escalation of lamotrigine should be necessary when

lamotrigine is added to the existing lopinavir/ritonavir therapy.

In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers,

the lamotrigine dose may need to be increased if lopinavir/ritonavir is added, or decreased if

lopinavir/ritonavir is discontinued. Plasma lamotrigine monitoring should be conducted before and

during 2 weeks after starting or stopping lopinavir/ritonavir, in order to see if lamotrigine dose

adjustment is needed (see section 4.5).

Elderly (above 65 years)

No dosage adjustment from the recommended schedule is required. The pharmacokinetics of

lamotrigine in this age group do not differ significantly from a non-elderly adult population (see

section 5.2).

Renal impairment

Caution should be exercised when administering /…/ to patients with renal failure. For patients with

end-stage renal failure, initial doses of lamotrigine should be based on patients' concomitant medicinal

products; reduced maintenance doses may be effective for patients with significant renal functional

impairment (see sections 4.4 and 5.2).

Hepatic impairment

Initial, escalation and maintenance doses should generally be reduced by approximately 50% in

patients with moderate (Child-Pugh grade B) and 75% in severe (Child-Pugh grade C) hepatic

impairment. Escalation and maintenance doses should be adjusted according to clinical response (see

section 5.2).

Method of administration

/…/ dispersible tablets may be chewed, dispersed in a small volume of water (at least enough to cover

the whole tablet) or swallowed whole with a little water.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use

Skin rash

There have been reports of adverse skin reactions, which have generally occurred within the first eight

weeks after initiation of lamotrigine treatment. The majority of rashes are mild and self-limiting,

however serious rashes requiring hospitalisation and discontinuation of lamotrigine have also been

reported. These have included potentially life- threatening rashes such as Stevens–Johnson syndrome

(SJS), toxic epidermal necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic

Symptoms (DRESS); also known as hypersensitivity syndrome (HSS) (see section 4.8).

In adults enrolled in studies utilizing the current lamotrigine dosing recommendations the incidence of

serious skin rashes is approximately 1 in 500 in epilepsy patients. Approximately half of these cases

have been reported as Stevens–Johnson syndrome (1 in 1000). In clinical trials in patients with bipolar

disorder, the incidence of serious rash is approximately 1 in 1000.

The risk of serious skin rashes in children is higher than in adults. Available data from a number of

studies suggest the incidence of rashes associated with hospitalisation in children is from 1 in 300 to 1

in 100.

In children, the initial presentation of a rash can be mistaken for an infection, physicians should

consider the possibility of a reaction to lamotrigine treatment in children that develop symptoms of

rash and fever during the first eight weeks of therapy.

Additionally the overall risk of rash appears to be strongly associated with:

- high initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine

therapy (see section 4.2)

- concomitant use of valproate (see section 4.2).

Caution is also required when treating patients with a history of allergy or rash to other AEDs as the

frequency of non- serious rash after treatment with lamotrigine was approximately three times higher

in these patients than in those without such history.

All patients (adults and children) who develop a rash should be promptly evaluated and /…/

withdrawn immediately unless the rash is clearly not related to lamotrigine treatment. It is

recommended that /…/ not be restarted in patients who have discontinued due to rash associated with

prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk. If the patient

has developed SJS, TEN or DRESS with the use of lamotrigine, treatment with lamotrigine must not

be re-started in this patient at any time.

Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern

of systemic symptoms including fever, lymphadenopathy, facial oedema, abnormalities of the blood

and liver and aseptic meningitis (see section 4.8). The syndrome shows a wide spectrum of clinical

severity and may, rarely, lead to disseminated intravascular coagulation and multiorgan failure. It is

important to note that early manifestations of hypersensitivity (for example fever, lymphadenopathy)

may be present even though rash is not evident. If such signs and symptoms are present the patient

should be evaluated immediately and /…/ discontinued if an alternative aetiology cannot be

established.

Aseptic meningitis was reversible on withdrawal of the drug in most cases, but recurred in a number of

cases on re- exposure to lamotrigine. Re-exposure resulted in a rapid return of symptoms that were

frequently more severe. Lamotrigine should not be restarted in patients who have discontinued due to

aseptic meningitis associated with prior treatment of lamotrigine.

There have also been reports of photosensitivity reactions associated with lamotrigine use (see section

4.8). In several cases, the reaction occurred with a high dose (400mg or more), upon dose escalation or

rapid up-titration. If lamotrigine-associated photosensitivity is suspected in a patient showing signs of

photosensitivity (such as an exaggerated sunburn), treatment discontinuation should be considered. If

continued treatment with lamotrigine is considered clinically justified, the patient should be advised to

avoid exposure to sunlight and artificial UV light and take protective measures (e.g. use of protective

clothing and sunscreens).

Haemophagocytic lymphohistiocytosis (HLH)

HLH has been reported in patients taking lamotrigine (see section 4.8). HLH is characterised by signs

and symptoms, like fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy,

cytopenias, high serum ferritin, hypertriglyceridaemia and abnormalities of liver function and

coagulation. Symptoms occur generally within 4 weeks of treatment initiation, HLH can be life

threatening.

Patients should be informed of the symptoms associated with HLH and should be advised to seek

medical attention immediately if they experience these symptoms while on lamotrigine therapy.

Immediately evaluate patients who develop these signs and symptoms and consider a diagnosis of

HLH. Lamotrigine should be promptly discontinued unless an alternative aetiology can be established.

Clinical worsening and suicide risk

Suicidal ideation and behaviour have been reported in patients treated with AEDs in several

indications. A meta- analysis of randomised placebo-controlled trials of AEDs has also shown a small

increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the

available data do not exclude the possibility of an increased risk for lamotrigine.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate

treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical

advice should signs of suicidal ideation or behaviour emerge.

In patients with bipolar disorder, worsening of depressive symptoms and/or the emergence of

suicidality may occur whether or not they are taking medications for bipolar disorder, including /…/.

Therefore patients receiving /…/ for bipolar disorder should be closely monitored for clinical

worsening (including development of new symptoms) and suicidality, especially at the beginning of a

course of treatment, or at the time of dose changes. Certain patients, such as those with a history of

suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of

suicidal ideation prior to commencement of treatment, may be at a greater risk of suicidal thoughts or

suicide attempts, and should receive careful monitoring during treatment.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing

the medication, in patients who experience clinical worsening (including development of new

symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are

severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Hormonal contraceptives

Effects of hormonal contraceptives on lamotrigine efficacy

The use of an ethinyloestradiol/levonorgestrel (30 μg/150 μg) combination increases the clearance of

lamotrigine by approximately two-fold resulting in decreased lamotrigine levels (see section 4.5). A

decrease in lamotrigine levels has been associated with loss of seizure control. Following titration,

higher maintenance doses of lamotrigine (by as much as two-fold) will be needed in most cases to

attain a maximal therapeutic response. When stopping hormonal contraceptives, the clearance of

lamotrigine may be halved. Increases in lamotrigine concentrations may be associated with dose-

related adverse events. Patients should be monitored with respect to this.

In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal

contraceptive that includes one week of inactive treatment (for example "pill-free week"), gradual

transient increases in lamotrigine levels will occur during the week of inactive treatment (see section

4.2). Variations in lamotrigine levels of this order may be associated with adverse effects. Therefore,

consideration should be given to using contraception without a pill-free week, as first-line therapy (for

example, continuous hormonal contraceptives or non-hormonal methods).

The interaction between other oral contraceptive or HRT treatments and lamotrigine have not been

studied, though they may similarly affect lamotrigine pharmacokinetic parameters.

Effects of lamotrigine on hormonal contraceptive efficacy

An interaction study in 16 healthy volunteers has shown that when lamotrigine and a hormonal

contraceptive (ethinyloestradiol/levonorgestrel combination) are administered in combination, there is

a modest increase in levonorgestrel clearance and changes in serum FSH and LH (see section 4.5). The

impact of these changes on ovarian ovulatory activity is unknown. However, the possibility of these

changes resulting in decreased contraceptive efficacy in some patients taking hormonal preparations

with lamotrigine cannot be excluded. Therefore patients should be instructed to promptly report

changes in their menstrual pattern, i.e. breakthrough bleeding.

Dihydrofolate reductase

Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase, hence there is a possibility of

interference with folate metabolism during long-term therapy (see section 4.6). However, during

prolonged human dosing, lamotrigine did not induce significant changes in the haemoglobin

concentration, mean corpuscular volume, or serum or red blood cell folate concentrations up to 1 year

or red blood cell folate concentrations for up to 5 years.

Renal failure

In single dose studies in subjects with end stage renal failure, plasma concentrations of lamotrigine

were not significantly altered. However, accumulation of the glucuronide metabolite is to be expected;

caution should therefore be exercised in treating patients with renal failure.

Patients taking other preparations containing lamotrigine

/…/ should not be administered to patients currently being treated with any other preparation

containing lamotrigine without consulting a doctor.

Brugada-type ECG

Arrhythmogenic ST-T abnormality and typical Brugada ECG pattern has been reported in patients

treated with lamotrigine. The use of lamotrigine should be carefully considered in patients with

Brugada syndrome.

Development in children

There are no data on the effect of lamotrigine on growth, sexual maturation and cognitive, emotional

and behavioural developments in children.

Precautions relating to epilepsy

As with other AEDs, abrupt withdrawal of /…/ may provoke rebound seizures. Unless safety concerns

(for example rash) require an abrupt withdrawal, the dose of /…/ should be gradually decreased over a

period of two weeks.

There are reports in the literature that severe convulsive seizures including status epilepticus may lead

to rhabdomyolysis, multiorgan dysfunction and disseminated intravascular coagulation, sometimes

with fatal outcome. Similar cases have occurred in association with the use of lamotrigine.

A clinically significant worsening of seizure frequency instead of an improvement may be observed.

In patients with more than one seizure type, the observed benefit of control for one seizure type should

be weighed against any observed worsening in another seizure type.

Myoclonic seizures may be worsened by lamotrigine.

There is a suggestion in the data that responses in combination with enzyme inducers is less than in

combination with non-enzyme inducing antiepileptic agents. The reason is unclear.

In children taking lamotrigine for the treatment of typical absence seizures, efficacy may not be

maintained in all patients.

Precautions relating to bipolar disorder

Children and adolescents below 18 years

Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviour

in children and adolescents with major depressive disorder and other psychiatric disorders.

Excipient(s)

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per dispersable tablet, that is to say

essentially ‘sodium-free’.

Sulphites (E220-E228)

May rarely cause severe hypersensitivity reactions and bronchospasm.

4.5

Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

Uridine 5'-diphospho (UDP) glucuronyl transferases (UGTs) have been identified as the enzymes

responsible for metabolism of lamotrigine. Drugs that induce or inhibit glucuronidation may,

therefore, affect the apparent clearance of lamotrigine. Strong or moderate inducers of the cytochrome

P450 3A4 (CYP3A4) enzyme, which are also known to induce UGTs, may also enhance the

metabolism of lamotrigine.

Those drugs that have been demonstrated to have a clinically significant impact on lamotrigine

metabolism are outlined in Table 6. Specific dosing guidance for these drugs is provided in Section

4.2.

Table 6: Effects of other medicinal products on glucuronidation of lamotrigine

Medicinal products that

significantly inhibit

glucuronidation of lamotrigine

Medicinal products that

significantly induce

glucuronidation of lamotrigine

Medicinal products that do not

significantly inhibit or induce

glucuronidation of lamotrigine

Valproate

Phenytoin

Carbamazepine

Phenobarbitone

Primidone

Rifampicin

Lopinavir/ritonavir

Ethinyloestradiol/

levonorgestrel

combination**

Atazanavir/ritonavir*

Oxcarbazepine

Felbamate

Gabapentin

Levetiracetam

Pregabalin

Topiramate

Zonisamide

Lithium

Buproprion

Olanzapine

Aripiprazole

Lacosamide

Perampanel

*For dosing guidance (see section 4.2)

**Other oral contraceptive and HRT treatments have not been studied, though they may similarly

affect lamotrigine pharmacokinetic parameters (see sections 4.2 and 4.4).

There is no evidence that lamotrigine causes clinically significant induction or inhibition of

cytochrome P450 enzymes. Lamotrigine may induce its own metabolism but the effect is modest and

unlikely to have significant clinical consequences.

Interactions involving antiepileptic drugs

Valproate, which inhibits the glucuronidation of lamotrigine, reduces the metabolism of lamotrigine

and increases the mean half-life of lamotrigine nearly two-fold. In patients receiving concomitant

therapy with valproate, the appropriate treatment regimen should be used (see section 4.2).

Certain AEDs (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce

cytochrome P450 enzymes also induce UGTs and, therefore, enhance the metabolism of lamotrigine.

In patients receiving concomitant therapy with phenytoin, carbamazepine, phenobarbitone or

primidone, the appropriate treatment regimen should be used (see section 4.2).

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. These

events usually resolve when the dose of carbamazepine is reduced. A similar effect was seen during a

study of lamotrigine and oxcarbazepine in healthy adult volunteers, but dose reduction was not

investigated.

There are reports in the literature of decreased lamotrigine levels when lamotrigine was given in

combination with oxcarbazepine. However, in a prospective study in healthy adult volunteers using

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. 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).

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.

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.

Potential interactions between levetiracetam and lamotrigine were assessed by evaluating serum

concentrations of both agents during placebo-controlled clinical trials. These data indicate that

lamotrigine does not influence the pharmacokinetics of levetiracetam and that levetiracetam does not

influence the pharmacokinetics of lamotrigine.

Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin

(200 mg, 3 times daily) administration. There are no pharmacokinetic interactions between lamotrigine

and pregabalin.

Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of

lamotrigine resulted in a 15% increase in topiramate concentrations.

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.

Plasma concentrations of lamotrigine were not affected by concomitant lacosamide (200, 400, or 600

mg/day) in placebo-controlled clinical trials in patients with partial-onset seizures.

In a pooled analysis of data from three placebo-controlled clinical trials investigating adjunctive

perampanel in patients with partial-onset and primary generalised tonic-clonic seizures, the highest

perampanel dose evaluated (12 mg/day) increased lamotrigine clearance by less than 10%. An effect

of this magnitude is not considered to be clinically relevant.

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.

Evidence from in vitro studies indicates that lamotrigine does not displace other AEDs from protein

binding sites.

Interactions involving other psychoactive agents

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.

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.

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. An effect of this magnitude is not generally expected to be

clinically relevant. Lamotrigine at 200 mg did not affect the pharmacokinetics of 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. 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.

In a study of 18 adult patients with bipolar I disorder, receiving an established regimen of lamotrigine

(100-400 mg/day), doses of aripiprazole were increased from 10 mg/day to a target of 30 mg/day over

a 7 day period and continued once daily for a further 7 days. An average reduction of approximately

10% in Cmax and AUC of lamotrigine was observed. An effect of this magnitude is not expected to be

of clinical consequence.

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. These experiments also suggested that metabolism of lamotrigine was

unlikely to be inhibited by clozapine, fluoxetine, phenelzine, risperidone, sertraline or 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.

Interactions involving hormonal contraceptives

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. 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). 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).

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. 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. 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. 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). 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.

Interactions involving other medicinal products

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. In patients receiving

concomitant therapy with rifampicin, the appropriate treatment regimen should be used (see section

4.2).

In a study in healthy volunteers, lopinavir/ritonavir approximately halved the plasma concentrations of

lamotrigine, probably by induction of glucuronidation. In patients receiving concomitant therapy with

lopinavir/ritonavir, the appropriate treatment regimen should be used (see section 4.2).

In a study in healthy adult volunteers, atazanavir/ritonavir (300 mg/100 mg) administered for 9 days

reduced the plasma AUC and Cmax of lamotrigine (single 100 mg dose) by an average of 32% and

6%, respectively. In patients receiving concomitant therapy with atazanavir/ritonavir, the appropriate

treatment regimen should be used (see section 4.2).

Data from in vitro assessment demonstrate that lamotrigine, but not the N(2)-glucuronide metabolite,

is an inhibitor of Organic Transporter 2 (OCT 2) at potentially clinically relevant concentrations.

These data demonstrate that lamotrigine is an inhibitor of OCT 2, with an IC50 value of 53.8 µM. Co-

administration of lamotrigine with renally excreted medicinal products, which are substrates of OCT 2

(e.g. metformin, gabapentin and varenicline), may result in increased plasma levels of these medicinal

products.

The clinical significance of this has not been clearly defined, however care should be taken in patients

co- administered with these medicinal products.

4.6

Fertility, pregnancy and lactation

Risk related to antiepileptic drugs in general

Specialist advice should be given to women who are of childbearing potential. The antiepileptic

treatment should be reviewed when a woman is planning to become pregnant. 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.

Monotherapy should be preferred whenever possible because therapy with multiple AEDs could be

associated with a higher risk of congenital malformations than monotherapy, depending on the

associated antiepileptics.

Risk related to lamotrigine

Pregnancy

A large amount of data on pregnant women exposed to lamotrigine monotherapy during the first

trimester of pregnancy (more than 8700) do not suggest a substantial increase in the risk for

major congenital malformations, including oral clefts. Animal studies have shown developmental

toxicity (see section 5.3).

If therapy with /…/ is considered necessary during pregnancy, the lowest possible

therapeutic dose is recommended.

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. Intake of

folic acid when planning pregnancy and during early pregnancy may be considered.

Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There

have been reports of decreased lamotrigine plasma levels during pregnancy with a potential risk of

loss of seizure control. After birth lamotrigine levels may increase rapidly with a risk of dose-related

adverse events. Therefore lamotrigine serum concentrations should be monitored before, during and

after pregnancy, as well as shortly after birth. 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. In addition, dose-related undesirable effects should be monitored after birth.

Lactation

Lamotrigine has been reported to pass into breast milk in highly variable concentrations, resulting in

total lamotrigine levels in infants of up to approximately 50% of the mother's. Therefore, in some

breast-fed infants, serum concentrations of lamotrigine may reach levels at which pharmacological

effects occur.

The potential benefits of breast-feeding should be weighed against the potential risk of adverse effects

occurring in the infant. Should a woman decide to breast-feed while on therapy with lamotrigine, the

infant should be monitored for adverse effects, such as sedation, rash and poor weight gain.

Fertility

Animal experiments did not reveal impairment of fertility by lamotrigine (see section 5.3).

4.7

Effects on ability to drive and use machines

As there is individual variation in response to all AED therapy, patients taking /…/ to treat epilepsy

should consult their physician on the specific issues of driving and epilepsy.

No studies on the effects on the ability to drive and use machines have been performed. 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. In clinical trials

with lamotrigine adverse reactions of a neurological character such as dizziness and diplopia have

been reported. Therefore, patients should see how /…/ therapy affects them before driving or operating

machinery.

4.8

Undesirable effects

The undesirable effects for epilepsy and bipolar disorder indications are based on available data from

controlled clinical studies and other clinical experience and are listed in the table below. Frequency

categories are derived from controlled clinical studies (epilepsy monotherapy (identified by†) and

bipolar disorder (identified by §)). Where frequency categories differ between clinical trial data from

epilepsy and bipolar disorder the most conservative frequency is shown. However, where no

controlled clinical trial data are available, frequency categories have been obtained from other clinical

experience

The following convention has been utilised for the classification of undesirable effects:- Very common

(≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000);

very rare (<1/10,000), not known (cannot be estimated from the available data).

System Organ Class

Adverse Event

Frequency

Haematological abnormalities

including neutropenia,

leucopenia,

anaemia, thrombocytopenia,

pancytopenia,

aplastic anaemia,

agranulocytosis

Very rare

Haemophagocytic lymphohistiocytosis (see

section 4.4)

Very rare

Blood and

lymphatic

system

disorders

Lymphadenopathy

Not known

Immune System

Disorders

Hypersensitivity syndrome

(including such

symptoms as,

fever, lymphadenopathy, facial

oedema, abnormalities of the

blood and liver,

disseminated intravascular coagulation,

multi

organ failure).

Very Rare

Hypogammaglobulinaemia

Not known

Aggression, irritability

Common

Confusion, hallucinations, tics

Very rare

Psychiatric Disorders

Nightmares

Not known

Headache

†§

Very Common

Somnolence

†§

, dizziness

†§

, tremor

insomnia

agitation

Common

Ataxia

Uncommon

Nystagmus

Rare

Unsteadiness,

movement

disorders,

worsening

Parkinson's

disease

extrapyramidal

effects,

choreoathetosis

increase

in seizure frequency

Very Rare

Nervous System

Disorders

Aseptic meningitis (see section 4.4)

Rare

Diplopia

, blurred vision

Uncommon

Eye disorders

Conjunctivitis

Rare

Gastrointestinal

disorders

Nausea

, vomiting

, diarrhoea

, dry mouth

Common

Hepatobiliary disorders

Hepatic failure, hepatic dysfunction

increased liver function

tests

Very rare

Skin rash

5†§

Very common

Alopecia, photosensitivity reaction

Uncommon

Stevens–Johnson Syndrome

Rare

Toxic epidermal necrolysis

Very rare

Skin and

subcutaneous

tissue

disorders

Drug Reaction with Eosinophilia and Systemic

Symptoms

Very rare

Arthralgia

Common

Musculoskeletal and

connective tissue

disorders

Lupus-like reactions

Very rare

General disorders

administration

site

conditions

Tiredness

, pain

, back pain

Common

Description of selected adverse reactions

Haematological abnormalities and lymphadenopathy may or may not be associated with the

hypersensitivity syndrome (see Immune system disorders).

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. The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to

disseminated intravascular coagulation and multiorgan failure. It is important to note that early

manifestations of hypersensitivity (for example fever, lymphadenopathy) may be present even though

rash is not evident. If such signs and symptoms are present, the patient should be evaluated

immediately and /…/ discontinued if an alternative aetiology cannot be established.

These effects have been reported during other clinical experience.

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.

Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases

have been reported without overt signs of hypersensitivity.

In clinical trials in adults, skin rashes occurred in up to 8-12% of patients taking lamotrigine and in

5-6% of patients taking placebo. The skin rashes led to the withdrawal of lamotrigine treatment in 2%

of patients. The rash, usually maculopapular in appearance, generally appears within eight weeks of

starting treatment and resolves on withdrawal of /…/ (see section 4.4).

Serious potentially life-threatening skin rashes, including Stevens–Johnson syndrome and toxic

epidermal necrolysis (Lyell's Syndrome) and drug reaction with eosinophilia and systemic symptoms

(DRESS) have been reported. 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).

The overall risk of rash, appears to be strongly associated with:

- high initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine

therapy (see section 4.2)

- concomitant use of valproate (see section 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).

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in

patients on long-term therapy with lamotrigine. The mechanism by which lamotrigine affects bone

metabolism has not been identified.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare

professionals are asked to report any suspected adverse reactions via the national reporting system

listed in Appendix V.

4.9

Overdose

Symptoms and signs

Acute ingestion of doses in excess of 10 to 20 times the maximum therapeutic dose has been reported,

including fatal cases. Overdose has resulted in symptoms including nystagmus, ataxia, impaired

consciousness, grand mal convulsion and coma. QRS broadening (intraventricular conduction delay)

has also been observed in overdose patients. Broadening of QRS duration to more than 100 msec may

be associated with more severe toxicity.

Treatment

In the event of overdose, the patient should be admitted to hospital and given appropriate supportive

therapy. Therapy aimed at decreasing absorption (activated charcoal) should be performed if indicated.

Further management should be as clinically indicated. There is no experience with haemodialysis as

treatment of overdose. 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).

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: other antiepileptics, ATC code: N03AX09.

Mechanism of action

The results of pharmacological studies suggest that lamotrigine is a use- and voltage-dependent

blocker of voltage gated sodium channels. 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). These effects are likely to contribute to the anticonvulsant properties of 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.

Pharmacodynamic effects

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

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.

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.

Clinical efficacy and safety

Clinical efficacy and safety in children aged 1 to 24 months

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. Treatment was initiated

in 177 subjects, with a dose titration schedule similar to that of children aged 2 to 12 years.

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). 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. Dose reductions of up to

90% were required in some patients at the end of week 2. Thirty-eight responders (> 40% decrease in

seizure frequency) were randomised to placebo or continuation of 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. The difference was not statistically significant: 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. 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%).

Clinical efficacy and safety in Lennox-Gastaut syndrome

There are no data for monotherapy in seizures associated with Lennox-Gastaut syndrome.

Clinical efficacy in the prevention of mood episodes in patients with bipolar disorder

The efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder has

been evaluated in two studies.

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. 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). The

primary endpoint was "Time to Intervention for a Mood Episode (TIME)", where the interventions

were additional pharmacotherapy or electroconvulsive therapy (ECT). 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. The results are shown in Table 7.

Table 7: Summary of results from studies investigating the efficacy of lamotrigine in the prevention of

mood episodes in patients with bipolar I disorder

‘Proportion’ of patients being event free at week 76

Study SCAB2003

Bipolar I

Study SCAB2006

Bipolar I

Inclusion

criterion

Major depressive episode

Major manic episode

Lamotrigine

Lithium

Placebo

Lamotrigine

Lithium

Placebo

Intervention

free

0.22

0.21

0.12

0.17

0.24

0.04

p-value Log

rank test

0.004

0.006

0.023

0.006

Depression

free

0.51

0.46

0.41

0.82

0.71

0.40

p-value Log

rank test

0.047

0.209

0.015

0.167

Free of

mania

0.70

0.86

0.67

0.53

0.64

0.37

p-value Log

rank test

0.339

0.026

0.280

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.

The efficacy of lamotrigine in combination with mood stabilisers has not been adequately studied.

Children (10-12 years of age) and Adolescents (13-17 years of age)

A multicentre, parallel group, placebo-controlled, double-blind, randomised withdrawal study,

evaluated the efficacy and safety of lamotrigine IR as add-on maintenance therapy to delay mood

episodes in male and female children and adolescents (age 10-17 years) who had been diagnosed with

bipolar I disorder and who had remitted or improved from a bipolar episode while treated with

lamotrigine in combinations with concomitant antipsychotic or other mood- stabilising drugs. The

result of the primary efficacy analysis (time to occurrence of a bipolar event – TOBE) did not reach

statistical significance (p=0.0717), thus efficacy was not shown. In addition, safety results showed

increased reporting of suicidal behaviours in lamotrigine treated patients: 5% (4 patients) in the

lamotrigine arm compared to 0 in placebo (see section 4.2).

Study of the effect of lamotrigine on cardiac conduction

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. There was no clinically significant effect

of lamotrigine on QT interval compared to placebo.

5.2

Pharmacokinetic properties

Absorption

Lamotrigine is rapidly and completely absorbed from the gut with no significant first-pass metabolism.

Peak plasma concentrations occur approximately 2.5 hours after oral administration of lamotrigine.

Time to maximum concentration is slightly delayed after food but the extent of absorption is

unaffected. There is considerable inter-individual variation in steady state maximum concentrations

but within an individual, concentrations rarely vary.

Distribution

Binding to plasma proteins is about 55%; it is very unlikely that displacement from plasma proteins

would result in toxicity.

The volume of distribution is 0.92 to 1.22 L/kg.

Biotransformation

UDP-glucuronyl transferases have been identified as the enzymes responsible for metabolism of

lamotrigine.

Lamotrigine induces its own metabolism to a modest extent depending on dose. 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.

Elimination

The apparent plasma clearance in healthy subjects is approximately 30 mL/min. Clearance of

lamotrigine is primarily metabolic with subsequent elimination of glucuronide-conjugated material in

urine. Less than 10% is excreted unchanged in the urine. Only about 2% of lamotrigine-related

material is excreted in faeces. Clearance and half-life are independent of dose. The apparent plasma

half-life in healthy subjects is estimated to be approximately 33 hours (range 14 to 103 hours). In a

study of subjects with Gilbert's Syndrome, mean apparent clearance was reduced by 32% compared

with normal controls but the values are within the range for the general population.

The half-life of lamotrigine is greatly affected by concomitant medicinal products. Mean half-life is

reduced to approximately 14 hours when given with glucuronidation-inducing medicinal products

such as carbamazepine and phenytoin and is increased to a mean of approximately 70 hours when co-

administered with valproate alone (see section 4.2).

Linearity

The pharmacokinetics of lamotrigine are linear up to 450 mg, the highest single dose tested.

Special patient populations

Children

Clearance adjusted for body weight is higher in children than in adults with the highest values in

children under five years. The half-life of lamotrigine is generally shorter in children than in adults

with a mean value of approximately 7 hours when given with enzyme-inducing medicinal products

such as carbamazepine and phenytoin and increasing to mean values of 45 to 50 hours when co-

administered with valproate alone (see section 4.2).

Infants aged 2 to 26 months

In 143 paediatric patients aged 2 to 26 months, weighing 3 to 16 kg, clearance was reduced compared

to older children with the same body weight, receiving similar oral doses per kg body weight as

children older than 2 years. The mean half-life was estimated at 23 hours in infants younger than 26

months on enzyme-inducing therapy, 136 hours when co-administered with valproate and 38 hours in

subjects treated without enzyme inducers/inhibitors. The inter-individual variability for oral clearance

was high in the group of paediatric patients of 2 to 26 months (47%). The predicted serum

concentration levels in children of 2 to 26 months were in general in the same range as those in older

children, though higher Cmax levels are likely to be observed in some children with a body weight

below 10 kg.

Elderly

Results of a population pharmacokinetic analysis including both young and elderly patients with

epilepsy, enrolled in the same trials, indicated that the clearance of lamotrigine did not change to a

clinically relevant extent. After single doses apparent clearance decreased by 12% from 35 mL/min at

age 20 to 31 mL/min at 70 years. The decrease after 48 weeks of treatment was 10% from 41 to 37

mL/min between the young and elderly groups. In addition, pharmacokinetics of lamotrigine was

studied in 12 healthy elderly subjects following a 150 mg single dose. The mean clearance in the

elderly (0.39 mL/min/kg) lies within the range of the mean clearance values (0.31 to 0.65 mL/min/kg)

obtained in nine studies with non-elderly adults after single doses of 30 to 450 mg.

Renal impairment

Twelve volunteers with chronic renal failure, and another six individuals undergoing hemodialysis

were each given a single 100 mg dose of lamotrigine. Mean clearances were 0.42 mL/min/kg (chronic

renal failure), 0.33 mL/min/kg (between hemodialysis) and 1.57 mL/min/kg (during hemodialysis),

compared with 0.58 mL/min/kg in healthy volunteers. Mean plasma half-lives were 42.9 hours

(chronic renal failure), 57.4 hours (between hemodialysis) and 13.0 hours (during hemodialysis),

compared with 26.2 hours in healthy volunteers. On average, approximately 20% (range = 5.6 to 35.1)

of the amount of lamotrigine present in the body was eliminated during a 4-hour hemodialysis session.

For this patient population, initial doses of lamotrigine should be based on the patient's concomitant

medicinal products; reduced maintenance doses may be effective for patients with significant renal

functional impairment (see sections 4.2 and 4.4).

Hepatic impairment

A single dose pharmacokinetic study was performed in 24 subjects with various degrees of hepatic

impairment and 12 healthy subjects as controls. The median apparent clearance of lamotrigine was

0.31, 0.24 or 0.10 mL/min/kg in patients with Grade A, B, or C (Child-Pugh Classification) hepatic

impairment, respectively, compared with 0.34 mL/min/kg in the healthy controls. Initial, escalation

and maintenance doses should generally be reduced in patients with moderate or severe hepatic

impairment (see section 4.2).

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology,

repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproductive and developmental toxicity studies in rodents and rabbits, no teratogenic effects but

reduced foetal weight and retarded skeletal ossification were observed, at exposure levels below or

similar to the expected clinical exposure. Since higher exposure levels could not be tested in animals

due to the severity of maternal toxicity, the teratogenic potential of lamotrigine has not been

characterised above clinical exposure.

In rats, enhanced foetal as well as post-natal mortality was observed when lamotrigine was

administered during late gestation and through the early post-natal period. These effects were observed

at the expected clinical exposure.

In juvenile rats, an effect on learning in the Biel maze test, a slight delay in balanopreputial separation

and vaginal patency and a decreased postnatal body weight gain in F1 animals were observed at

exposures approximately two- times higher than the therapeutic exposures in human adults.

Animal experiments did not reveal impairment of fertility by lamotrigine. Lamotrigine reduced foetal

folic acid levels in rats. Folic acid deficiency is assumed to be associated with an enhanced risk of

congenital malformations in animals as well as in humans.

Lamotrigine caused a dose-related inhibition of the hERG channel tail current in human embryonic

kidney cells. The IC50 was approximately nine-times above the maximum therapeutic free

concentration. Lamotrigine did not cause QT prolongation in animals at exposures up to

approximately two-times the maximum therapeutic free concentration. In a clinical study, there was no

clinically significant effect of lamotrigine on QT interval in healthy adult volunteers (see section 5.1).

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Heavy magnesium carbonate

Microcrystalline cellulose

Povidone

Hydroxypropyl cellulose

Saccharine sodium

Crospovidone

Magnesium stearate

Guar gum

Black currant flavour

(containing Maltodextrin, Acacia, Triacetin, Lactic acid, Maltol, Ethyl alcohol, Acetic acid, Propylene

glycol and Sulphites)

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

2 mg: 18 months.

5 mg: 21 months.

25 mg, 50 mg, 100 mg and 200 mg: 2 years.

6.4

Special precautions for storage

2 mg: Blister: Do not store above 30°C. Plastic tablet container: This medicinal product does not

require any special storage conditions.

5 mg: Do not store above 30 °C.

25 mg, 50 mg, 100 mg and 200 mg: This medicinal product does not require any special storage

conditions.

6.5

Nature and contents of container

Blister packs (Al/PVDC): 7, 10, 20, 21, 28, 30, 40, 42, 50, 50x1, 56, 60, 98, 98x1, 100, 100x1 and 200

dispersible tablets.

2 mg plastic tablet containers (PP): 30 and 100 dispersible tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

7.

MARKETING AUTHORISATION HOLDER

<[To be completed nationally]>

{Name and address}

<{tel}>

<{fax}>

<{e-mail}>

8.

MARKETING AUTHORISATION NUMBER(S)

<[To be completed nationally]>

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:

29 October 2004

Date of latest renewal:

29 October 2009

<[To be completed nationally]>

10.

DATE OF REVISION OF THE TEXT

<[To be completed nationally]>

08-April-2021

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