KPATKA XAPAKTEPI4CTIIKA HA TIPOAYKTA

1, I'ME HA JIEKAPCTBEHI{fl IIPOAYKT

MEKCIlfl HaqarlHa onaKoBKa 5 mg, 10 mg, 15 mg, 20 mg Su:ruupaur't ra6 r+n" ?/,g 1Y 91? /, ,

MEXTA initiation pack 5 mg, 10mg, 15 mg,20 mg film-coated tablets l8f :p 0$ :ll ?015 l

j

2. KAqECTBEH I,I KOJII4TIECTBEH C:bCTAB

Bcrxa @lr.nuupana ra6,rerxa cl4tpNa 5 mg, l0 -mg, 15 mg, 20 mg ueuaHT[HoB xriapox;lopl'{4, e(B[BaJIeHrHrina 4,15 mg, 8j1 mg, t2,46 mg, 16,62 mg ueudirrnn.

floN,toutHo eeuecrgo c l.{reecrHo neilcrsue:3a MEKCI4-{ l0 mg Qunnupaun ra6,rerru:Jlarrosa N{orloxt 4par................82,83 mg

3a rb,'rn[q cnr.rcbK Ha noMorqHl4Te BeurecrBa Bl-{xre roqra 6.1

3. ,TIEKAPCTBEHA @OPMA

@ununpana ra6nerra.@n:ruqpaHrlre ra6,lerKu or 5 mg ca 6eln ,4o noqrr 6e:ru ora,luo-lpo4mroaaru tpuluupauz ta6lerxn,

rpaBxpaHri c "5" or eanara crpana.@nluupaunre ra6;rer1n or l0 mg ca 6e:ru Ao noqru 6oru npognrroaarrl Qrururlpanu ra6,rerrlt, crecHeHll B

cpeaar4 Aaoiino I{3nr'KHalI-I, c aerureilHa rlepra or aBsre crpanu na ra6lexara.<Dn,'rvupamlre ra6lerKl,1 or 15 mg ca opaHxeBx, oBaJrHo-rrpoA6JlroBaru QurllupaHlr ra6lerxu, rpaBupaHl'I c

"l5" or e.{Hara crpaHa.@luunpannre ra6,'rerxu or 20 mg ca 6neaouepaenn oBaJIHo-npoAT,JIroBaru $trrunpanu ta6,'rerrn,

rpanupaHu c "20" or eaHa crpaHa.

4. IT,'II,IHI,ITI HI4 AAHHI{

4.1 Tepanenruvuu[oKa3aHriq

JleqeHr.re Ha nauueHTI4 c yMepeHa Ao rexra ctenes na 6orem na AruxafiMep

4.2 ,{osuponxa lt HaquH Ha rlpuroxeHne

Jle.reHuEro rpl6na Aa 6tAe sanoqHaTo u Ha6,rroAasaHo oT leKap c onliT B AuarHocTllqupaHero n reqeHl.IeTo

Ha AeMeHUUTTa Ha AnqxafiMep. ,rleveHuero rpabna 6r,ge:alovaauo, caMo aKo r,rMa n[uer KoeTo aa ce fpHxr.r

:a 6o.nHur rz peaoBHo aa cJreA[ nprreMa Ha reKapcrBeHur rrpoayKT or nau[eHTa. ,[uarno:ara rpr6na.qa 6rAe

[ocraBeHa B cborBercrBr,Ie cr,c cgBpeMeHHlrre ,qLIarHocrI-IqH[ npt{Htll{nu. floHoctlMocrfa r,t ao3l-IpaHero Ha

uelraurnu rpr6ra,{a ce npeorreHrBa perynrpHo, 3a npeanoql.{raHe B paMKure Ha 3 ueceua clea 3anoqgane ua

neqeHlero. C:rea rosa. KJrr.tHltr{Hara nor3a or MeMaHTnH I-I rIoHocLrMocTTa Ha naqr'IeHTa KIM neqeHueTo,

cJreABa.{a ce lpeoqeH{Ba perynrpHo, B c'boTBsTcTBr.re c aKTyalHHTe xJr}.lH14.lH11 p6KoBoAcraa. Ilog.4rpxaqoro

Ier{eHue MOXe Aa npOAbJIXI{, AOKaTO TepaneBTltqHa nOI3a e 3aAOBOJII'ITeIHa u IaUUeHTT,T IIOHaCt JleqeHxeTo

c MeMaHTnH. Axo ca ua Jrr-irle AoKa3areJlcrBa 3a or[aAaHe Ha repafleBTl-rt{Ht eOeKT I4,'1u aKo naqlIeHTT,T He

noHacr JleqeHhero, rpr6aa ga ce o6ttlItcJII'I nperpartBaHe Ha JleqeHuero c MeMaHTI'IH.

MEKCht rpr6aa aa ce flpr4nara Be.[Hbx,[HeBHo. no eaHo 14 cl,tuo Bpe]\4e ua aerr. @l,rqlpantlte ta6,rerrr

uoNe 4a 6r4ar npueunu c mrlr 6ea xpana.

.IIo:nDogxa

Buspacmuu:

Tumpupaue ua dosamarlpelopl'rnaHara uaualna go:a e 5 mg aHeBHo, Kotro rrocrerreHHo ce yBenr.rqaBa npe3 nrpalpe 4 ceguuqlr orJreqeHneTo, 3a.qa ce aocrrzrHe npenopbqBaHaTa no'4nrpxa la ao3a KaxTo cneaBa:

CeAurua I (aeu 1-7):|Iaqaenmr rpx6ra ga npueua elua Qr.r:rvupaua ra6rsrKa MEKCIL{ or 5 mg ,4HeBHo (6ejlt,r Ao no.]ru 6en11,oBarHo-rrpoAlJrroBarlr) n upoguxenue ua 7 qnu.

Ceavzqa 2 (aeu 8- l4):llaquenrrr rpx6ra 4a nprieMa eaHa 0r. rMr40aHa ra6rerxa MEKCI,{JI or 10 mg gneauo (6legoxuru 4oNr,,rrlr, c oralua Qopva) n npoatlNesue sa7 agu.

Ce4lrr.rqa 3 (aen l5-21):llaulreumr rpx6ra aa npueMa eAua $ruuupaua ra6ner*a MEKCI4JI or 15 mg anenno (opauNenz, oBarrHo-npog:r,rronaru) a npogrnNeurze ua 7 4uu.

Ceavnua 4 (neH 22-28):flaqlrenrrr rpr6ra ga np'eMa eaHa Qlrrr'arzpaxa ra6:rgrxa MEKCI4fl or 20 mg .4uenuo (6.ne4ovepeenu,oBa;rHo-npoAl,JrroBaru) r npo4nrxenue na 7 nnu.

Maxclrua:ruara 4lresua ao:a e 20 mg IHeaHo,

Ifodz,pacat4a dosaIlpeloprvranma noarpNaura.qoga e 20 mg aneauo.

Cneuza,r Hr nonylaullrIlaqueumu e cmapsecKq 6b3pacmBr: ocHoaa Ha K,rr-rH'qHr,rre [poyqBaHrir, npenop'r{BaHara AHeBHa Ao3a 3a naqr{eHT, Ha Ba3pacr Ha,q65 rogltrra e 20 mg 4uerno (20 mg ae4ulN gneauo), rarro e noco.reHo no-rope.

.neuq u nuoutuYnorpe6ara na MEKCZ{ npu reqa Ha B63pacr noa lg roaunu He ce npenopbqBa, nopaa[ Jrr,tnca Ha aaHHr4orsocno 6egonacsocrra u eQnxacuoctra,

Bu6peuuo yepetcdaueIIpz naqneHur c JIeKo yBpeaeHa 6t6pevua Synrqr]r (rpearnar.rHoB Xnr4pbHc 50-80 ml/min) He ce Hajraraa"4anrfipaHe Ha ao3ara. Ipz laqlremu c yMepeHo 6r6pe.ruo yBpexAaHe (xpearltrnuoa uxprnc 30-49 ml/min) .qHeBHara go:a rpx6oa ga 6r,ge 10mg. flpn ao6pa noHocliMocr creA Hafi_Marxo 7 AHeBHoJleqeHr{e, Ao3ara MoNe la 6:rge yne.nuveua 1o 20 mg/gen, cr,fJracHo oraHAaprHara cxeMa ua rtrrpupaHe. llpr.rraqlleHrl'r c rexKo 6r'6pevno yrpeN4ane (rpearununoa rcrlrprnc 5-29 ml/min) Auelnara gosa rps6"a aa 6"ael0 mg.

Ve pu od p o 6u o yep e ctcd a u erlpu nauueuru c JreKo u'rrz yMepeHo HapyrneHa .repuo4po6na Qyuxqr.rr (r<.nac A r.r B no child-pugh.1 He eueo6xogttt'lo aAamripaHe Ha.{o3ara, HrMa ,4aHHr.r :a ynorpe6ara Ha M9MaHTHH np11 nau[eHTr{ c rexKo'repHo4po6uo yBpex(AaHe. He ce npenop:rvBa rrpr.rJroxeHr4ero na MEKCIIII npr naqr"rr,

" ,"^no

vepHoapo6no yopeNaane.

Haqug na npuloNenrzeIlepopa,rno npu:roNenue.

4.3 llporlrBonofta3aHus

Cnplxvyncranrelnocr K6M axrltBHoro BeluecrBo IuII.I KbM HrKoe a.r. uoMorrIHI,ITeTo.rKa 6.1.

BetrlecrB4 lr:6poeHra n

4.5

4.4 Cnequa,rsu npeAynpexAeHuq n [peArra3Hu Mepxu npu ynorpe6a

flpenopr,vaa ce lloBlrueHo BHHMaHHe npli nauneHTr.r c er,anencva, aHaMHe3a 3a rapqoBe r.rJrr{ naurieHrri cnpeApa3noJramrlx Qaxropn sa enrcrenclrr.

Tpr6na aa ce lrs6fina eAHoBpeMeHHara ynorpe6a Ha aHTaroHlrcrtl na N-uern:r-D-acnaprar (NMDA), raroaMaHraarrH, KeraMr.tH llnr.r AeKcrpoMeropQan. Terz *egr.rHeHru AeiicrBar B:bpxy cbu{ara peqelropHa c[sreMaKaro MeMaHTI.IH, LI cJIeAoBareJIHo HexellaHure pearqurl (cnr,p:anr4 rJraBHo c ueHTpalrHara HepBHa chcreMa(I{HC)) uoxe aa 6r,,Aar no-qecrr.r rr no-clr.mro uspa:euu (ax. ro-rxa 4.5).

H.rxou r[arropu, Kor{To Moxe Aa noBr.rr]Jar fi ua ypuuara (rx. roura 5.2 .,EnriMnHnpaHe"), uoNe gaHaJroxar BHHMarerHo npocireMBaHe Ha rrauuema. Te:u Qaxropu BKrrcr{Bar ,qpacrriqHrl npoMeHu B .{rrsrara,HanpI.IMep or MecHa KGM BercraprraHcKa 4lder4 wrr4 Macr.rBeH nprreM Ha aJrKanr.r3ripaul{ crouarunu 6y$epu,Ocaen roea pH ua )?ItHara Moxe Aa ce noBIIruI rplt c'bcrofirlrx na 6:r6peuna ry6y:rapua aqnAosa (ETA) lfirlrtexrl,l untlerqlrz na orAeJrr.ITeJIHara crrcreMa c Proteus bacteria,

B nogeqero KJrIrHLtqHIr npoyqBaHl.rt naueHTI{ crc cropo npeKapaH lrn$apm ua vlrorapa4 Aer(oMneHc[paHa:acroilna cbpaeqHa Heaocrarr,qHogr (rrac no NYHA III-IV) ruru HeKoHTponupaHa xznepronur ca 6r,rnLl3xrIor{eHI.I. BcreAcrsue Ha ToBa IIMa caMo ofpaHIiqeHI-I .{agHLI It naqueHTliTe c raKxBa cbcTotHltr rp.g6sa Aa6T 4ar npoc.negrnaHu BHriMarerHo

MEKCI4TI c6A6pxa naKTo3a MoHoxrr,{paT. fIaqIaeHT[ c peAKr4 HacneAcTBeuu npo6.nevu Ha raJraKro3HaHe[oHocl4Mocr, Lapp laxra:en aeQlrqnr nnu rjlloKo3o-raJraKTo3na ua:ra6cop6qlrx ne rp.r6na Aa rrprreMarTOBa JreKapcTBO.

Brauuogeficrnue c Apyrn Jrer€pcrBeHn npoAyKTu H Apyru oopMI| Ha B3a[MoAeiicrBu€

flopaan $apuarolorfiqHnre e(berTu x uexauu:ua Ha 4eficrBue Ha MeMaHTr.rH, Mo)Ke aa B63Hr{KHar crcaHure'naalrno4eficrnua:

- Haquncr Ha aeficrB[e AaBa ocHoBaHI.I{ Aa ce npe.{noraf4 ue eQexrnre Ha L-aona. AonaMHHepr[qHrrrearoHltcrll rI aHTuxoJlnHeprttqHure cpeAcrBa Moxe Aa 6'r,Aar 3acr{reH[ npu eAHoBpeMeHHo Jrer{eHrie caHTaroHr4crr.r aa NMDA Karo MeMaHTriH, EQercnre ua 6ap6urypalnle u HeBporenrr4uure Moa<c aa6raar nauanenu. E.4uonpeueunoro npl'I;IoxeHr.re Ha MeMaHTuH u cna3MoJrr.rrr.rqHrl cpercrBa, AaHTponeHu,ru 6ar:ro@en uoxe Aa r-r3MeHu AeicrBr.rero uM r.r roBa Aa Haroxrz Kopr{ rpaHe Ha ao3ara,

- EnHoBpeMeHHara ynorpe6a Ha MeMaHTr.rH 14 aMarra4r.rH rpr6na 4a ce ug6qrsa nopa,qr,r pltcK orSapuarororcnvxa ncuxo:a. 14 ABere cbeAuHeHr.rr npeAcraBnrBar xr.tMLrqHo cpoAHr,r aHTaroH[cr[ HaNMDA. CtrUoro Moxe Aa ce orHact sa KeraMltH r.t .IexcrpoueropQan (ex. roura 4.4). Ily6:ruxyuau eenl,tH K[[HrrreH cryrafi sa neporren pucn n npu nou6unaqirra Ha MeMaHTun u r]enlrrouu.

- Apyrtr aKTIzBHI4 BelqegrB4 Karo IrLrMErIrnI.IH, paHITILIALIH, npoKar4HaMr.r.q, xI4HIraIrH, xrrHr,IH I{ Hlr(orlrH,rr3rIoJBBauIi cr,rqara 6r6pevna cucreMa 3a Karr.rorreH TpaHcnopr KaKTo aMaHTaar.rH, e B1,3MoxHo AaB3AIAMOAEfiCIBAT C MEMAHTI4H, KOETO BO.{I.I AO NOT9HIII,a[eH pI{cK oT TIoBI{I]]a3aHe Ha ua3MeHI,ITe HI,IBa.

- Llma BepotrHocr 3a noHHxaBa.He Ha cepyMHoro Hr]Bo Ha xr.rlpoxJroporua3r.rr (HCT), r<oraro MeMaHTuHce lpnnara eAHoBpeueuuo c HCT lrnu c xoublruaqlrr, rorro sxrto.{na HCT.

- B nocruapxerr.{HroBrlr onrlr r.{Ma cro6rqeulu 3a ri3o;tr{paHr4 cn1nrafi Ha noBlrueHo MexAyHapo,qnoHopMaJIH3I{paHo oTHo[IeHIle (INR) npu naql{eHTn, Korrro ca neKyBaHr.r eAHoBpeMeHHo c aapQaplln.Buperz ve He e ycraHoBeHa rlpriquHHo-cJreAcrBeHa Bp63K4 npenop:bqrjrelHo e BHItMareJrHorIpocJIeAsBaHe Ha nporpolr6nnonoro BpeMe I. rn INR nplr naqlrenrra, Koltro ce JreKyBar e.qHoBpeMeHHo cnepopzurH[ aHTr-.rKoaIyJ]aHTr,l.

flpu SapuaroruncrlrqHr.r npoyqBaHr.rr npu e,qHoKparHa lo3a npu Mn4qu 3ApaBn 4o6poeorqn ne cena6ffo,Eagar 3HaqIrMI.I B3alrMo,{eftcrnlrr ueN4y aKTI.rBHr.rre BerqecrBa Ha MeMaHTuH n r:rlr6yplrg/Msr$opNlrxrI-IJII-I .IIOHCNCSHJI.

B x:ruulrqso npofrBaHe rrprr MJraArr 3ApaBr.r nuqa ne ce na6lro4ana :uavuu eSerr Ha MeMaHTriH BT,pxy

$apuarorunermara Ha raJraHTaMrrH.

Mevanrnn ne uuxlr6upa in yitro cYP 1A2, 2A6, 2C9, 2D6, 281' 3A' $nanuH-clAlpxaqaraMoHooKchreHa34 en o Kc ltll- x l4.tlpo,l a3ara luu cylQonr.rpaxero'

4.6 <Deprulnrer. 6peMeHHocr l l KbpMeHe

bpeMeHHocrFI""u 'qunn":a 6per'rerrHu, neKyBaHH c MeMaHTl{H. flpoyuraunlra nplr xuBoTHI-I ca noKa3JII,t BT,3MoXHocT 3a

HaMa]IeHoBl,TpeMaToqHopa3BI-,ITlrenpuHI,IBaHaeKcno3ll l l l l ' ,KoHTocaH.{eHTI,lqHIlI lJIuJIeKo3aBIIIxeHricnprMo eKcno3r,rquflTa lpu uoaera (nx. rour<a 5.3). floteuqualHllsr pllcK npl4 xopa He e tl3BecreH.

Mevanrr.rs He rpr6aa aa ce usno:rssa npu 6peueHroct, ocBeH B cryqaii Ha KareroplaqHa HeooxoAlrMocr

Krpu.gqqHe e LI3BecrHo aanr4 MeMaHTI.TH 09 eKcKpeTI-Ipa c qoBeIIKoTo MJltKo, Ho KaTo ce IIMa npegru4 :runotprnuocrra

Ha BeIqecTBoTo, ToBa e TBbpae B:b3MoxHO. xeUrme, KorrTo nplleMaT MeuaHtun, tre tpr6aa aa KbplvltT.

4.7 Er[exru stpxy cnoco6socrra:a uror[lifoaue u pa6ora c maurunn

yMepeHa ao Texxa cTe[eH ua 6o.necr Ha AnuxafiMep o6tlruoneno BoAl,t ,uo Hapy ena cnoco6sosr :a

uoQrpane r.r BJro raBa cnoco6nocma :a pa6ora c MaIIII,IHII. oCSeH rOsa, MEKCII{ IIOBJII'jI'Ba B neKa Ao

y""p"ru "r"n"n

cnoco6Hocrra sa oQnpaue Ir pa6ora c MaIIIIHI4, TaXa LIe aU6ylaropnure naqnenrra rpl6ra

aa 6rgar npe4ynpexaaBaHu aa BHllMaBar MHoro'

4.8 Hexe,ranu,rexapcrBeHupeaKurr[

B Klr.rHn.{Hr4 npoy.{BaHr{r npn JIeKa Ao rexKa AeMeHqIlt, BKrIoqBa .lI4 I 784 naquesur, :reKyBaHI{ c MeMaHTIIH

u 1 595 naulreHrra, Tperl4paHlr c nraqe6o, o6ulara 'lecrora Ha HexeraHlrte JIeKapcrBeHI.r peaKIIn[ npu

MeMHTI,IH He Ce pa3nlrqaBa oT Ta3I4 npr.{ uaue6o, raro HexeJIaHI-ITe JreKapcTBeH[ peaxqlru o6uxnoaeno ca

,JreKI_t ao yMepeHtl no Texegl. Haii-qecTo IIotBtBaluI{Te ce HexeJIaIIu JIeKapcTBeHlr peaKIII{U C IO-BI{COKa

qecToTa B fpynaTa Ha,{erleHrie c MeMaHTHH, OTKOIIKOTO B fpynaTa Ha JIeqeHI'Ie c maue6o, ca 3aMaJIHOCT

f"""t"*"t'0,:X cpeuy 5,6Vo), r.naso6orue (5,2o/o cpeuy 5,io/o1, '-'"n (4,6% cpeiwy 2'6Vo)' c:"ttsrusoc;r

(3,4% cpewy 2,2%) n ancoxo r<pr,ruo uat'traue (4,lVo cpeuy 2'8Yo)'

Hexsrannre reKapcTBeHU peaKq[u, nocoqeHs s ra6r[IlaTa no-Ao.]ly, ca pef]'IcTpl4paHll IIO BpeMe Ha

K;tr.{Hr,rrrHn flpoyqBaH[r c MeMaHTI.IH I4 cneA nycKaHero My Ha rla3apa. IIpI.l BctKo fpylupaHe B 3aBr'Icl4Mocr or

qecrorar4 HexeJraHlITe JlerapcrBeHll pearuru ce nr6porBar B Hl{3xoatu pea no orHouleHlre Ha rexecrra'

HexenaHLITe IeXapcIBeHu peaKrlllu ca KaTefoptBIIpaHH cbfjlacHo cI'IcTeMo-opmHHI'I KJIaCOBe' KaTO Ce

r8nor3Ba cjreAHara KoHBeHrtun: MHOfo qecrn (>l/10), vecrn (>l/100 ao <l/10), Heuecrn (zlll 000 ao

<1/100) ,pe .qxr . r (> l /100004o< l /1000) ,MHofopeAKI I (<1 /10000] ,cHeI .EBecTHaqectora(orHaI I - I I IH I , ITe

aaHHu He Moxe aa 6tne uanpanena oqeura)'

CncreMo-opraHHfi K,racoBe: {ecrora: Hexe,raHa,rerapcrBeHa PeaK[t,tq:

a+\\a', t >s/r(s

I,Indexuuu u undecraqun Heqecru lr,6nqru.r usder<uru

Hapyureum na uuyHHara cllcreMa 9ecrn Crplxvysc'rnnre.nHocr K6M

reKapcTBa

IIcrfil,lqHH HapyueHlrt 9ecrnHeqecrr,r

C Heu3nectHa qegrora

CtHnusocrO6rpranocrXalroqunaultr'

flcuxorlrquu peaxutlu2

HapyueHut Ha HePBHara cl.IcreMa qecrr.i

Heqecrr.rMHoro peaKl.r

3a ra.sHocrHapy[eHa noxoAKafbP'IoBe

CrpaeuHn tapyuetu.lg He.rec a Crp.Aeuua ne4ocraruqnocr

Cr4oan uapYuenu-r r{ecrnHe.recrfi

XnneproHI.I'Beno:Ha rpo116osa./rpoM6oeNr6o,'Il-r:bIu

Pecnl-lparopHx, rpbattu t'I r{ecrH ,{ncnner

ffi

Me,{uacTlHaJHI{ HapylxeHl'It

Crouan no-vpeen n HaPYIneHrrt 9ecrnHeqecruC HelnsecrHa qecrora

3anexfloapnqaneI laHKpearI4T-

O6uu uapyurenrlx u e$erru Ha urcroroHa npJ4roxeHxe

rlecruHeqecru

fraso6orHeYMopa

rx-;au"*u^a * *6tam*"lt HIaBHo nplr naqtleHru c reNra $opua na 6onecrra ua Alqxaiillep'' llIzotrwpau cttylari, cbo6ulasaHl{ n rocrMapKeruHfoBlit orrl'1T'

EorecrTa Ha AnrHafiMep ce cBr,p3Ba C AerlP€Cr4r, CyIIqHAHI4 l/E:e]'1l U Otllr'ttl 3a CaMOy6UiiCTBo. B

nocTMapKeTuHroBr.tt o11uT TaKuBa C;ryqau ce cr,ofirqanar npu naurreHTl-{, JIeKyBaHI4 C MeMaHTI-lH,

Cro6rqanane na HexeJraHu peaKqrirl

AKO noJlyqnTe HTKaKBU HexeJraHr4 peaKrlnr4, yBeaoMeTe BaIllu .nerap r.ur.r Qapuaqenr. Toaa lxlloqBa BcIi'{Kti

B.b3MOXHI{, HeO[UCaHr4 B Ta3r.r JusIOBKa Hexenaq!{ pearqlrlr, MONere C}XIO Aa C'bO6rq}ITg HeXeJIaI 4 peaKllllll

guperrHo na I'bnuHI'ITeJIHa areHU[t no [eKapcrBara (I4AJI):

E:bJIfAPI4II, CoQnr 1303, y:r. [ar'rru fpyen 8

Te:r. +359 2 8903555e,r. noua: bda@bda.bsye6cafir: www.bda.bg

Karo clo6uasare HexeJIaHI.'t pearql.il{' Moxere aa Aaaere cBot npllHoc 3a noJIfIaBaHe Ha floBeqe

uuQopuaqur ornocso 6egonacnocrra Ha roBa reKapcrBo.

4.9 Ilpegorupane

,I,Iua orpanu'ren onfiT cbc cjryqan Ha rrpeao3l,IpaHe B KInHII[IHI4Te nporrBall[t I{ noctMapKeTuHfoBIu onxT.

Cuunmouu:clyuanre Ha orHocr4TeJrHo B[coKo npeAo3r.rpaHe (caoTBerHo 200 mg r.r 105 mg/aen 3a TpI.l aHI.I) Ce CBAp3Bar

r{Jru c-6c cnMllroMn Ha yMopa, cJla6ocx sJvnu A4apvs' urra nporl{qar 6elculrnrouno' B cnyvan na

npeao3r{paHe c ao3a no,{ 140mg ra:rr.r npu Heri3BecrHa ao3a npII naqIIeHTn Ce [potBtBaT cI.lMnroMI'ITe'

"uuprun, c l]HC (o6lpraHogT, cbHJrr{BoCT, COMHOJTeHTHOCT, CBerOBtpTeX, B636y,[4 afpecI.IBHOCT'

xaJrroqnHaqnu H Hapyruena noxo4ra) n/rurn c racrpounrecTnHaJleH npol.I3xo.q (nonptqane rz glrapnn).

B Hai-TexKn, cnyqan Ha npeao3trpaHe rrau[eHTlT e oqeJltn [p!I nepopa[eH nplieM Ha o6uto 2 000 mg

"a"unr"r " no"n"A"aq" eQe*rlr r"pxy I{HC (Io-lueana r<oMa c nocJleaBanla al.llrJronl;It I'r B!36yAa). B To3x

cryqafi nalrl4eHTar e JIeKyBaH cI.IMn;oMarHqHo r'r c n-na.r'aotlepe:a llaqlrenmr ce e nl:ctasogrur 6e:

.4r,;rorpainn nooregcrsu-x.

B 4pyr c.nyvafi na rllcoKo npeAo3lipaHe c nepopaJleH nplreu ua 40-0 mg MeMaHTI.TH naur'IeHTbr clrqo e oue;ltn

" "" " "urra*o"-. IIauueHfiT e rrMaJr cr{MnToMLI, CB}p3aHI.I C IIHC KaTO HeCnOKOiCTBO, IICIIXO34 3pl',IreflHl4

xa.nrcrIHHaULtX, npoKoHByJrclrBHocr, coMHOTeHTHOCT' CTynOp tI 6e3c63HaHlie'

Jle'reuue:B cny.rafi Ha rrpeao3r{paHe reqeHr.tsro rpr6aa 4a 6T4e cuunrouarurlHo. H.f,Ma cneqlion'leH aHTI'IAOT npll

,"tonar*uqt" t atp"4ortput". 3a orcrpaH'Baue Ha aKTllBHoTo BeuecTBO Ce npl'lJrafa craH'{aprHa Kjltlt{ltqHa

npoueayp4 Karo Ha[pI.{Mep croMa[IHa npoMI{BKa, aKTIzBeH Bb IeH (:a npeaornparxsane Ha loreHurraflHa

eHTepoxenaranHa peIIHpKyJIaIII4t)' noBljuaBaHe KuceJlljHlrocfia Ha yplrHara' 3acI'IJIeHa Anype3a'

B yqM Ha nprBHarl{ U Cr.tMru.oMn na o6rqo cnplxcruMynl{paHe Ha IIeHTpalHaTa HepBHa CI-rCTeMa (IIHC),

Tpt6Ba aa ce o6MI'IcJrL BHlIMareJIHo cl,IMnroMarllqHo KJITiH[rlHo JIer{eHue'

-1

5. @APMAKOJIOII{TIHI{CBOfrCTBA

5.1 (DapMaKoa[HaM[qHncBoiicrBa

OapMaKorepaneBrr.rvua rpyna: ,{pyrn neKapcrBa nporlrB aeMeHunt, ATC roa: N06DX0l.

Hapacraa 6por ua gora:arercrBara 3a roBa, qe HapyueHoro oyHKIrI,IoHIrpaHe Ha fJlyraMareprHqHaraHeBporpaHcMucur, no-KoHKperHo Ha peqemopure :a NMDA, gonplruacr raxro 3a nporBara Ha cr.rMnroMure,TaKa n 3a npofpecupaHero na 6o:recrra npLI HeBpoaereHeparrBHara aeMeHlrlrt.

MeMaHTr.rH e BoJrrrDx-3aB'rcr.rM, c yMepeH ar$unnier r.r HeKoHKypeHTeH NMDA-peqenropen auraronngr, TofiMo,{ynupa eoeKTATe Ha naroJror}rqHo noBHrrreH[Te roH}iqHr] Hr{Ba Ha ffyraMar4 Kol4To Moxe,qa AoBe,qar AoHapyrxeHo OyHKrrIaoHIrpaHe Ha HeBpoHI4Te.

Kttuuuuuu npoyueauuaB [poBeAeHo npof{BaHe c MoHorepalus npn tlyna [au[eHTr-I, crpaAaull4 or yMepeHa .4o rexl(a crerreH Ha6onecrra sa AnrxafiMep (n:xogen 06[r pe3ynrar or MlrHri r.r3cJreaBaHe Ha rcuxur{Hrlr craryc (mini mentalstate examination) (MMSE) npu ocHoBa 3 go 14) ca npocreAeHr4 06l{0 252 aM6ynaropHl{ naqlreHrl.I.flpoy.raanero aeMoHcrprrpa 6naronprrrunre eQexru or reqeHgero c MeMaHTrlH B cpaBHeHrie c n:raue6o srpo4urNeune ua 6 ueceqa (ana.rut na ra6;tn4aaaulrre cnyLrar 3a BneqarJleHlrero Ha KJII-IHI{IIIIcra 3a npoMJIHasa 6a-gara Ha pa3rcBop (the clinician's interview based impression of change) (CIBIC-plus): p = 0,025;cbBMecrHo npoyqBaHe Ha 6orecrra Ha AnuxafiMep - exe.qHesr i,{eftHocru (Alzheimer's disease cooperativestudy activities of daily living) (ADCS-ADLsev): p = 0,003; 6arepnx :a rexKl yBpexAaHua (severe

impairment battery) (SIB): p : 0,002).

flpu npoBe,{eHo npoyrrBaHe c MeMaHTLIH Karo MoHoreparuit [plr neKa ao yMepeHa greleH Ha 6orecrra HaArqxaiiuep (usxogeu o6rq MMSE-pe:yrrar npl.l ocHoBa l0 rc 22) ca o6xBaHarfi 403 naqlleura. EQermr

npu neKyB:rHr4Te c MeMaHTTH naul4eHTl4 e 6rtn grarl-|cru,{ecKn 3Haqr[4o no-ao6'bp B cpurBHeHxe c To3fi np]|neKyBaHLITe c n:raqe6o naq[eHTlt no orHoIrIeHIre Ha ocHoBHI{Te roqKLI: cKa:ra 3a oIIeHKa Ha 6onec'rra HaA,rqxaftuep (Alzheimer's disease assessment scale) (ADAS-cog) (p:0,003)

" a1319-plus (p = 0,004) npe:

24qa ceavw\a npfi nocneAHoro npoBeaeHo Ha6.nro4euue (last observation carried forward) (LOCF). Ilpu

Apyro npoyrtBaHe c MoHorepanlrr Ha JreKa ao yrrlepeua 6orecr na A:rqxaiiuep ca paH,4oMLI3I.IpaHu o6uo

470 raqueHrr.r (u:xoren o6u MMSE- p€yJrrar nprr oclrosa ll go 23). [pu npocneKrr4BHo aeOuHnpaHLItntpBlrqen aHalu3 npe: 24-ra ceauuua He e nocrl{rHara crarucrllqecKa 3Har{}rMocr Ha rtpBl.rqHa e$u(acHocr.

Ilpr.r uera-aua,rus Ha rraqrieHTn c yMepeHa ao rexKa creneH Ha 6o:recrra Ha A:rqxafiuep (o6q MMSE

crop <20) or [ecr rrnaqe6o-KoHTponrrpaH[, 6-ueceqnz npoyqBaHlrt, Qa:a III (arcrrcveaqlt npoyqBaHfit c

MoHorepanur u npoyqBaHr.rr npu naqrreHTr.r Ha rrocTorHHa Ao3a aqerlirxojrl.IHecTepa3Hll unxn6uropu) eycraHoBeHo, qe clruecrByBa crarllcrllqecKll rxawru eQem B noJl3a Ha reqeHuero c MeMaHT[H 3a

KofHurr4BHarq r.tro6a,'rHara lr $yurqlroua;ruara cQepa. flpu [aqueHTra c npl.iapyxaBalqo BJIoIxaBane BbB

Bcr.jqKr.rre rpu cQepr.r, pe3yJrrarrrre ca noKa3aJrri crarlrcruqecxlr rHa'rnu et[err or MeMarrrI.IH,

flpeaorBpargBarq BJrorraBaHero, Karo ABa n6TI,I noBeqe rperllpaHlt c ntraqe6o naqueHTn AeMoHcrp[parBllorlaBane BbB Bcll.{Kr.lre rpr4 c$epr.r n cparnerue c reKyBaH[Te c MeMaHTLtH flautrerirlt Ql% cpeuiy l1%,p <0,0001).

5.2 (DapuarorruerrvHtlcBoiicrBa

,4.6cop6uuqMeuanrun uva a6co:rrorna 6r,roHaJrnqHocr nplz6lu:urarno 100%. T.* e uex.qy 3 u 8 uaca. Hrua.qauun, uexpaHara noBJrrrsBa a6cop6qmra ua ueMaIrrLIH,

Pa:n peae,r e H lr e

,{Henrure 4o:rl or 20 mg Boarr ,qo craIIIroHapHI.r rura3MeHu KoHueHTpaunu Ha MeMaHTuH, Kor.rro Bapnpar or70 ao 150 ng/ml (0,5-l pmol) c roreMll LIHrepItHAI4BuAyanH[r parflrrv* Koraro ca npunaraHu AHeBHx ao3r.ror 5 ,qo 30 mg e r{3rrr.rcJreHo cpeAHo cborHo[enue qepe6pocnuualua revuocr/cepyu 0,52. O6eulr napa3npeae;reHr.re e npu6.nu:lrrerno l0l/kg. OKono 45% or xoJrrlqecrBoro MeMaHTr4H e cBbp3aHo c nlra3MeHr,rre

1*9Y'!##@3,rrr*

6elrsun.

BlroroaHc6opMauaqllpu vonexa oxoro 80% or rrr.rpKynnpaqltre Sopuli Ha MeMaHrr.rH ca ro4 t[opuara Ha rtxoAHoro

cbe,4[HeHue. frasume uera6oluru trpn qoBeKa ca N-3,5-4rluerll:r-rnyaaHTaH, r.r3oMepHara cuec na 4- lr 6-xr.tapoKcrr-MeMar{Tun u I -uurposo-3,5-anuerru-aaauasran. Huro e,qr.rH or re3r.r Mera6ormll He nporBrBaNMDA-aurarorucrr{qHa aKTr.rBHogr. He e orxpur qlrroxporu P 450 Kararr.t3l{paH Mera6onra3'bu in vitro,

flpu npoyreane c lepopaJrHo nprrlraraH loC-MevaHtlrn. cpeAHo 84% or Ao3ara ce Bb3craHoBrBar B paMxr..rreaa20 !.Hu, xaro noseqe or 99olo ce ercrpernpar nper 6r,6peqlrre.

ErlrurnrpalgMeMaHTr.rH ce eJrxMr.rHr{pa no MoHoeKcrroHeHull:urHa KpriBa c repMr4HaJreH t'7, or 60 .uo 100 uaca. flpu

,qo6poBorrlu c HopMalHa 666pevna $ynrqrz.r o6qrur rurnpr,nc (C1",) gocrura 4o 170 mllmin/l,13 m' u qacr

or o6rqrzr 6T 6pe,reH KJrr.rpr,Hc ce peanuaupa,rpe: ryby.napHa ceKpeulrJt.

Er6pevnn.ar o6meH sKrro.{sa crqo ry6y:rna pe:op6qu-r, Kosro BepotrHo ce ocbluecrBtBa or KarI.toH-TpaHcnoprnpaqu 6e,r:r,qs. Crereara na 6r6pevuo eJrnMuHr.rpaHe Ha MeMaHruH B ycnoBr.rtra Ha aJIKaJIHaypr.rHa Moxe aa 664e uauarena 7 ,qo 9 ntru (aN. rovra 4.4). A:rra:ru:upauero Ha yp[Hara Moxe aa ce abJIxIlHa Apacrl4qHl-t npoMeHll B aueTaT4 Ha[pLIMep oT MecHa KbM BeferapuaHcKa Ar.rera, uJrrr Ha MaclrBeH rrplreM HaanKalrrl3npautl croMa]xHn 6y0epx.

llunefiuocrllpoyvrauurra nplr ,{o6poBonu[ norasaar nuneftua QapuaKoKr..rHerrma B ao3oBr,rr ar{ana3oH or 10 ao 40 mg.

Bpr:xa daoMaroKIaHgrtlra/daoluaxoauHaMurallpn 4o:a 20 mg ueuanrnr AHeBHo HrrBara s qepe6pocnfiua.nHara reqHocr orroBaptr na crofinocrrak1 (k1:KoncraHTa Ha urxu6upane) na lreuamr,rrq rorro e 0,5 pmol a xopara na QpoHTaiHI,It atr npu r{oBeKa.

5.3 llpearc,runnqnu aaHH[ 3a 6e3o[acHocr

B xparxocpovnu npoyqBaH[r B6pxy flnbxoBe MeMaHTr.rH, rarro ,upyrure NMDA-aHraronlrcrn, npeAI43BxKBaHeBpoHalHa BaKyonu3arrur rr HeKpo3a (re:r.rr.r ua Olney) caMo creA Ao3r.r, Bo,qerlrz Ao BItcoKl{ nIIKoBII cepyMHI,I

xoHrreHTpaqnlt. Ararcux lr apyr[ rIpeKltrlHlrqHu nprnHarlu npeauecrBar BaKyonr{3aun{ra r nerpo:ara. Trfi

raro erlexrnre He ca ua6ruoaaeaun npu AT,nrccporrHu lpoyrrBasut npu rpx3aqll LI Herpr3arll4, KlI,IHIrqHara

BpG3Ka C Te3I{ pe3yJrTaTI-I JIIrnCBa.

llpu npoy'rnauza 3a roKcr,rqHocr ca na6no.qaranu npoMeHJr[BIr I]3MeHeHI.It B oqI.ITe rlp]r noBrapt lH ce,{o3lt

npfi rpx3aqr4 u Kyqera, Ho He rr npu MaiiMyHr.r. CnequQlrvHrre oQrarllo,romuun npe le,q[ B KJIITHLTIHIre

npoyqBaHr.rt c MeMaHT[H He pa3Kpt{BaT HI'IKaKBU OrrHU rBMeHgHt'lt.

flplr rpn:avn e ua6nroaaBaHa OocOo;rnnlrgo:a r 6eno4po6Hnre uarpoQaru nopaAlr HarpynBaHe Ha MeMaHrnH

B Jrl3o3oMnre, To:lr e$em e rro3Har or Apyru aKTr.rBHr4 Ber1ecrBa c KaTI,IoHHLI aurlu$lt:rnn croi:icrsa.

Bepoxrno ctrqecrByBa Bp63Ka Mexgy roBa HarpynBaHe n BaKyoJII.BaIIlItra, Ha6nroAaBaHa B 6elrlre 4po6ose.Torra eQerr e Ha6rroAaBaH caMo npu npsjraraHe Ha Br.rcoKr.r Aosl] npu rpn:aulr. Klunuvnara 3HarII'IMogr Ha

Te3[r pe3yJITaTI.I He e IBBeCTHa.

He e ycragoBeHa feHoroKcl,IqHocr Ha MeMaIITI,IH cJreA LI3cJIeABaHe no craHAaprHri MeroAIjKI-t. HqN'Ia AaHHI:a

KapUI{HofeHHocT npl-t AoxIIBoT-rrpo,4bJIxI{TeJIHII [poyqBaHl-It npI-I MI-.IIIKI4 n nrbxoBe. Meuagu,tfl ne e

TeparoreHeH nprr nnlxoBe r,r 3afir1u, 4opu r.r B Ao3u, roKcl4qHI.I :a uaiirara, u He ca ot6ersgaHu HexellaHlt

reKapcrBeHr.r peaKrlnrl Ha MeMaHTI.tH trpxy Qeprurmera. IIpu nItXoBe e OT6e[.maHo IIOH[xaBaHe Ha

{eraluoro pa3BI]TI-te npl4 HI.IBa Ha eKcno3l,Iq[t, Kor-rro ca UIeHTrrqHrr rlJIr,I MaJIKo rro-BtlcoKll oT Te3[ Ha

eKcno3r,ru[rra npu xopa.

6. OAPMAIIEBTI,{qHI4AAHHI4

6.1 Cnncr,x sa noMou.lHure BerrrecrBa

.fldpo ua ma6rcmxama;5 m e - 1 5 m e - 2 0 m eI leryno:a, uurporpncranua PH 302Crlruufiee,4r,roKc[,4, rorolrren 6essoaeuKpocxapr'le:rora narpraITanxMarne:uen creapar

10 meI {e.nyaosa, r'rmporpucra.nna PH 302Jlamo:a DC (Ludipress LCE: Jlarro:a MoHoxr.r.{par + flonrzgon 30)Cfirnunes,4uorcua, ro:ronqes 6e:go.qesTalrMarHe3ueB creapar

O6euexa ua ma6remxama:5 m g - l 0 m g(Du,'rMoBo norprlrr.re )!r 8 (Opadry Yl 7000 White):HPMC 2910 / Xunpoue.no:a 5 cp (E 464)Tlrranon anorcua (E l7l )Maxporo,r / PEG 400 (E 1521)

I 5 m e@uruono noxpnrne Nr 24 (Opadry Orange 20433245):HPMC 2910 / Xunpouero:a (E 464)Xu,qporcunponu:rqe,ry:ro:a (E 463)Tanr (E 553b)Tnraron graorclr.q (E l7l)Xere:eu oxorA, xrrc (E 172)FD&C xrrro Ns6/Crscer Nr,rro FCFA,ryuzuuea rar (E 110)Xene3en oxcua, uepneu (E 172)

20 mg@u,ruono norpurne J,ls 28 (Opadry Pink 20,434056):HPMC 2910 / XunpoMeno3a (E464)Xr4.4poKcl-rnponlrrlqoryro:a (E 463)Tanr (E 553b)Tnranon auorclta (E l7l )Xele:eu oxclrA, qepnen (E 172)XereseH oKcna, qepeu (E 172)

6.2 Hecrgruecrlrmocru

Henpruroxulro

6.3 Cpox na rolnocr

2 ronuuu

6,4 Cnequa,ruu yc"roenq Ha cr,xpaHeH[e

,{a ce clxpaurea ua Mrcro, HeaocrbnHo 3a aella.

ffi

Aa ce cbxpaHrBa B oplrfHHaJrHaTa onfioBKa.,{a ce crxpanrea nog 25oC.

6.5 Bn4 lr ctqr,pxaxue Ha orranoBxara

Erncreplr or npo:paquo PVC/PEPVDC/AI r!o:ruo, a:roxeHr.r B r(aproHeH pa3Aenr4rerr.

MEKCI{' Haqa,'Ha onaKoBKa 5mg, 10mg, l5mg, 20mg Qz,ruupanu ra6lerxu cr4rpNa o6qo28 su uupanu ra1tterKu, onaKoBaHrr B 4 6'-..pa/ 7 suslaupanu ri6nerrr,/ 6:rncrep, rarro c:regra:

7 $unuupauu ra6lerxr.r MEKCl{f 5 mg / I 6micrep7 Qu,rvr.rpaun ra6.nerrr MEKCI4JI l0 mg / I 6,rrc-rip7 SmrvupaHn ra6,rerrclr MEKCh-fl I5 mg / I 6,rrcrep7 $uttuupanu ra6lerru MEKCH-{ 20 mg / I 6lucrep.

6.6 Cnequa,rnu npeArra3H[ MepKu npH ui]xBr,pJsHe

Hxua cnerrltalgu tr3rlcKBagllr 3a IBXB:bDJrgHe.

Helr:nor:gaH[-f,t JIeKapcrBeH npoayKT nru orna,q'rrHrrre Marepll:urx or Hero rpr6Ba aa ceC'bOTBETCTBTiE C MECTHIZTE Ij3IICKBAHII'.

7. IIPI4TEXATEJI IIA PA3PEIIIEHI{ETO 3A YTIOTPEEA

HOEEN OAPMA EOOAOroronprcreH nrr Nl36l4l5 CoQur, Eorrapu.arc:l.: +359 2 962 62 80qaKc: +359 2 962 90 36e.n.noqa: info@nobelpha@a.bg

8. HOMEP(A) HA PA3PEIIIEHI{ETO 3A. YIIOTPEEA

20140t91

AATA HA IIbPBO PA3PEINABAHE/TIOAHOB{BAHE HA PA3PEII]EHI,IETO 34YIIOTPEEA

10. AATA HA AKTyAJII43|IPAHE HA TEKCTA

02/20t5

n3xBbpnrT B

q

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