Herceptin - ჰერცეპტინი 440მგ/20მლ 1 ფლაკონი

herceptini ®

HERCEPTIN

simsivnis sawinaaRmdego saSualeba

1. Semadgenloba  

aqtiuri nivTiereba: trastuzumabi

preparatis dozebi:

150 mg erTjeradi dozis flakoni Seicavs sainfuzio xsnaris koncentratis mosamzadebel fxvnils

liofilizebuli fxvnili TeTri an mkrTali-yviTeli Seferilobisaa. xsnari – gamWvirvale da uferoa

momzadebuli xsnari Seicavs trastuzumabis 21 mg/ml-s.

440mg mravaljeradi dozirebis flakoni Seicavs trastuzumabis liofilizebul fxvnils infuziuri xsnaris koncentratis mosamzadeblad

gamxsneli: saineqcio wyali antimikrobuli konservantis saxiT Seicavs 1.1% benzilis spirts.

liofilizebuli fxvnili TeTri an mkrTali-yviTeli Seferilobisaa. xsnari – gamWvirvle da uferoa

momzadebuli xsnari Seicavs trastuzumabis 21 mg/ml-s.

2. Tvisebebi da efeqtebi

efeqturoba

herceptinis monoTerapia gamoyenebuli iyo klinikur cdebSi HER2 hipereqspresirebadi metastazirebadi sarZeve jirkvlis kibos mqone pacientebisaTvis, romlebsac uSedegod CautardaT erTi an ori qimioTerapia

herceptini aseve iyo gamoyenebuli antraciklinTan da ciklofosfamidTan an paklitaqselTan kombinaciaSi pirveli rigis Terapiis saxiT ZuZus HER2 hipereqspresirebadi metastazirebadi kibos mqone qalebSi

ZuZus HER2 hipereqspresirebadi metastazirebadi kibos mqone pacientebSi herceptiniT monoTerapias meore da mesame rigis Terapiis saxiT Tan axlavs remisiis jamuri sixSire 15% da sicocxlis saSualo xangrZlivoba 13 Tve.

herceptinis gamoyeneba antraciklinTan da ciklofosfamidTan an paklitaqselTan kombinaciaSi pirveli rigis Terapiis saxiT ZuZus HER2 hipereqspresirebadi metastazirebadi kibos mqone qalebSi sarwmunod aumjobesebs dros daavadebis progresirebamde mxolod qimioTerapiasTan SedarebiT. avadmyofebSi, romlebic antraciklin Semcvel reJimebs Rebulobdnen dro daavadebis progresirebamde izrdeba 1.7 TviT (6.1-dan 7.8 Tvemde), xolo paklitaqseliT namkurnaleb pacientebSi – 3.9 TviT (3.0-dan 3.9 Tvemde). herceptinis daniSvna agreTve aumjobesebs pasuxs simsivnis mxridan da sicocxlis 1-wlian xangrZlivobas mxolod qimioTerapiasTan SedarebiT. antisxeulebi trastuzumabis mimarT gamovlinda 1 pacientSi, amasTan alergiis movlenebi am pacientSi ar aRniSnula.

2.1.  moqmedebis meqanizmi

trastuzumabi aris dnm warmoebuli humanizirebuli antisxeuli, romelic seleqtiurad urTierTqmedebs epidermuli zrdis faqtori 2 (HER2) ujredgare domenTan. antisxeuli miekuTvneba IgG klass, romelic Seicavs adamianis CarCo regionebs da anti-p185 HER2 antisxeulebis komplementarul-ganmsazRvrel ubnebs, romlebic ukavSirdebian HER2.

protoonkogeni HER2 an c-erB2 kodirebas ukeTebs erTeul transmembranul gadamtans, receptorismagvar cilas masiT 185 kDa,

romelic struqturulad axlosaa epidermuli zrdis faqtoris receptorTan. HER2 hipereqspresia aRiniSneba ZuZus pirveladi kibos SemTxvevaTa 25-30%-Si. rasac Tan axlavs HER2 cilis eqspresiis momateba simsivnis ujredebis zedapirze, ris Sedegad adgili aqvs HER2 receptoris konstitucionalur aqtivacias.

3. farmakokinetika

trastuzumabis farmakokinetika Seswavlili iqna ZuZus meastazirebadi kiboTi avadmyofebSi. preparatis Seyvanisas xanmokle infuziebis saxiT dozebSi 10, 50, 100, 250 da 500 mg kviraSi erTxel. misi farmakokinetika dozaze damokidebuli iyo. dozis gazrdisas izrdeboda naxevradgamoyofis periodi, xolo preparatis klirensi klebulobda. klinikur kvlevebSi trastuzumabis datvirTviTi dozis (4 mg/kg) da yovelkvireuli SemanarCunebeli dozis (2 mg/kg) Seyvanis Semdeg naxevradgamoyofis periodi saSualod 5.8 dRis toli iyo (diapazoni 1-32 dRe).

3.1. farmakokinetika gansakuTrebul SemTxvevebSi: asaki ar axdens zegavlenas trastuzumabis ganawilebaze.

xanSiSesuli pacientebi:

kvlevebiT dadgenilia, rom asaki aranair gavlenas ar axdens  trastuzumabis dispoziciaze (ix. `doza da miReba~)

4. Cvenebebi

ZuZus metastazirebadi kibos mqone pacientebis mkurnaloba, romlebsac aReniSnebaT simsivnis HER2 hipereqspresia:

1. a)monoTerapiis saxiT, Tu pacients daavadebis metastazirebadi stadiis gamo ukve miRebuli hqonda qimioTerapiis erTi an meti sqema.
2. b)paklitaqselTan kombinaciaSi, Tu pacients jer ar miuRia mkurnaloba daavadebis metastazirebadi stadiis gamo.

5. doza da miReba

herceptiniT mkurnalobis dawyebamde, savaldebuloa HER2  testireba

5.1. dozirebis standartuli reJimi

datvirTviTi doza 4 mg/kg 90-wuTiani infuziis saxiT. pacientebs unda daakvirdnen cxelebis, Semcivnebis an sxva infuziuri reaqciebis gamovlenis Taobaze. am simptomebis kupireba SesaZlebelia infuziis SeCerebiT. simptomebis kupirebis Semdeg SesaZloa infuziis ganaxleba.

Semdgomi doza: 2 mg/kg kviraSi erTxel. Tu winamorbedi doza kargad amtani iyo, maSin momdevno dozebis Seyvana SesaZlebelia 30-wuTiani infuziebis saxiT. (ix. gverdiTi efeqtebi)

preparatis intravenurad nakadurad Seyvana ar SeiZleba.

klinikur kvlevebSi pacientebi herceptins Rebulobdnen daavadebis progresirebamde.

dozis Semcireba

klinikuri kvlevebis mimdinareobisas herceptinis doza ar Semcirebula. qimioTerapiiT gamowveuli Seqcevadi mielosupresiis dros pacientebs SeuZliaT gaagrZelon herceptiniis miReba, amasTan daculi unda iyo qimioTerapiis dozis Semcirebis an gadavadebis wesebi.

5.2. dozireba gansakuTrebul SemTxvevebSi

xanSiSesuli pacientebi

klinikur kvlevebSi xanSiSesul pacientebSi herceptinis doza ar Semcirebula.

bavSvebi

herceptinis usafrTxoeba da efeqtianoba bavSvebSi ar dadgenila.

6. ukuCvenebebi

hipermgrZnobeloba trastuzumabis an preparatis nebismieri sxva komponentis mimarT.

7. sifrTxilis zomebi

herceptiniT mkurnaloba unda Catardes mxolod onkologis meTvalyureobis qveS. infuziis mimdinareobisas aucilebelia pacientebis dakvirveba Semcivnebis, cxelebis an infuziuri reaqciebis sxva simptomebis gamovlenis Taobaze.

herceptinis recipientebSi aRwerilia gulis funqciis darRvevis simptomebi (qoSini, xvela, Ramis qoSinis Setevebi, periferiuli SeSupeba, galopis samniSna ritmi, gandevnis fraqciis Semcireba). gulis SegubebiTi ukmarisoba herceptiniT mkurnalobisas SeiZleba mZime xasiaTis iyos da letaluri gamosavlis mizezi gaxdes, da agreTve SeiZleba ganapirobos kedlisamyoli Trombozis ganviTareba tvinis sisxlmomaragebis Semdgomi darRveviT. amitom gulis funqciis darRvevis mqone pacientebis mkurnaloba gansakuTrebuli sifrTxiliTaa saWiro. avadmyofebma sanam maT daeniSnebaT herceptini unda gaiaron saguldagulo kardiologiuri gamokvleva, romelic unda moicavdes anamnezis Segrovebas, fizikalur gasinjvas da qvemomoyvanilidan erT an met instrumental gamoklvevas – eleqtrokardiografia, eqokardiografia, MUGA skanireba. jerjerobiT ucnobia Tu romeli meTodia ufro adeqvaturi kardiotoqsiurobis ganviTarebis riskis jgufis pacientebis gamosavlenad. herceptiniT mkurnalobisas aucilebelia marcxena parkuWis gandevnis fraqciis Semowmeba. magram monitoringiT yovelTvis ar aris SesaZlebeli im pacientebis gamovlena, romelTac gulis funqciis darRveva ganuviTardeba. gandevnis fraqciis klinikurad mniSvnelovani Semcirebisas daJinebiT rekomendebulia herceptinis mkurnalobis SeCereba. gulis funqciis darRvevis mqone pacientebis daaxloebiT or mesameds utardeboda Sesabamisi medikamenturi mkurnaloba, romelmac gaaumjobesa pacientebis umravlesobis mdgomareoba. benzilis spirti, romelic konservantis saxiT Sedis baqteriostaturi wylis SemadgenlobaSi, toqsikur zemoqmedebas axdens axalSobilebsa da 3 wlamde bavSvebSi. benzilis spirtis mimarT hipermgrZnobelobis mqone pacientebisaTvis gamxsnelad gamoyenebuli unda iqnes wyali ineqciebisaTvis, amasTan TiTeuli flakonidan unda gamoyenebuli iyos mxolod erTi doza. darCenili preparati unda iqnes gadagdebuli.

8. orsuloba da laqtacia

Cynomolgus-is jiSis maimunebze Catarebuli reproduqtiulma kvlevebma, rodesac gamoyenebuli doza adamianis yovelkvireul SemanarCunebel dozas (2 mg/kg) 25-jer aRemateboda, ar gamovalines reproduqtiulobis darRvevis an nayofze damazianebeli moqmedebis niSnebi. Tumca, adamianebSi reproduqtiuli toqsiurobis Sefasebisas aucilebelia mRrRnelebisTvis damaxasiaTebeli HER2 receptoris tipis mniSvnelobis gaTvaliswineba embrionis normaluri ganviTarebisas, agreTve gasaTvaliswinebelia embrionis daRupvis SemTxvevebi mutantur TagvebSi, romelTac aseTi receptori ar hqondaT. nayofis ganviTarebis adreul (orsulobis 20-50 dRe) da gvian (120-150 dRe) stadiebze aRiniSneboda trastuzumabis mier placentaruli barieris gadalaxva. ucnobia SeuZlia Tu ara herceptins damazianebeli zegavlena iqonios nayofze an reproduqtiolobaze. vinaidan cxovelebze Catarebuli reproduqtiolobis kvlevebi yovelTvis ar iZlevian adamianze zegavlenis prognozirebis saSualebas, umjobesia moveridoT herceptinis gamoyenebas orsulobis dros, Tu ra Tqma unda Terapiis potenciuri sargebeli dedisaTvis ar gadawonis SesaZlo risks bavSvisaTvis. gadadis Tu ara trastuzumabi dedis rZeSi ucnobia. vinaidan adamianis IgG sekretirebs dedis rZeSi, xolo SesaZlo damazianebeli moqmedeba bavSvze ucnobia, umjobesia pacientebi moeridon ZuZuTi kvebas herceptiniT mkurnalobis dros.

9. gverdiTi movlenebi

9.1. klinikuri kvlevebiT miRebuli gamocdileba

klinikuri kvlevebiT miRebuli gamocdileba

monacemebi gverdiTi movlenebis Sesaxeb mopovebuli iyo herceptinis klinikur kvlevebSi, rodesac preprati rekomendebuli dozirebis reJimSi gamoiyeneboda monoTerapiis saxiT, an kombinaciaSi antraciklinebis rigis preparatebTan (doqsorubicini an epirubicini) plus ciklofosfamidi, an paklitaqselTan. am kvlevebidan gamomdinare, pacientTa 50%-s SeiZleba aReniSnos gverdiTi efeqtebi, romelTan yvelaze xSiria infuziasTan dakavSirebuli  simptomebi, rogoricaa cieb-cxeleba. es simptomebi, rogorc wesi, mohyveba xolme herceptinis pirvel infuzias

herceptinTan dakavSirebiT, uaryofiTi reaqciebi aReniSna or aRniSnul kvlevaSi monawile pacientTa ≥10%-s. es reaqciebi exeboda Semdegs: 

organizmi mTlianad: tkivili muclis areSi, asTenia, tkivili welis areSi,  cxeleba, Semcivneba, Tavis tkivili,  

kuW-nawlavis traqti:  diarea,  gulisreva, Rebineba.

Zval-kunTovani sistema: saxsrebis tkivili, kunTebis tkivili.

kani da misi danamatebi:  gamonayari.

herceptinTan dakavSirebiT, uaryofiTi reaqciebi aReniSna or aRniSnul kvlevaSi monawile pacientTa raodenobis 1-dan 10%-mde  es reaqciebi exeboda Semdegs: 

organizmi mTlianad: tkivili muclis areSi, asTenia, tkivili welis areSi,  cxeleba, Semcivneba, Tavis tkivili, hipermgrZnobelobiTi reaqciebi

gul-sisxlZarRvTa sistema: vazodilatacia. nivTierebaTa cvlis darRveva: SeSupeba.

kuW-nawlavis traqti:  anoreqsia, konstipacia, dispefsia

limfopaTuri: leikopenia

metaboluri: periferiuli edema, edema

Zval-kunTovani sistema: saxsrebis tkivili 

nervuli sistema: SfoTva, depresia, Tavbrusxveva, Zilianoba, uZiloba, paresTezia.

sunTqvis organoebi: faringiti, riniti, sinusiti, sisxldena cxviridan, asTma, xvelis gaZliereba, qoSini, filtvebis dazianeba, plevraluri gamonadeni.

urogenitaluri: saSarde traqtis infeqcia

kani da misi danamatebi:  pruritusi, oflianoba, kanis simSrale, alopecia, ferimWamelebis gaCena, makulopapularuli gamonayari

brma SerCeviT Catarebul sxva klinikur kvlevebSi, mkerdis metastazuri kibos mqone pacientebi Rebulobdnen docetaqsels herceptinTan erTad an mis gareSe. qvemoT cxrilSi mocemulia gamovlenili arahematologiuri uaryofiTi efeqtebi, romlebic gamouvlinda kvlevaSi monawile pacientTa ≥10%-s:

infuziuri reaqciebi: herceptinis pirveli infuziis mimdinareobisas pacientebis 40%-s uviTardeba simptomkompleqsi, romelic ufro xSirad vlindeba SemcivnebiT da cxlebiT. rogorc wesi, es simptomebi sustad an zomieradaa gamoxatuli. simptomkompleqsi iSviaTad iwvevs infuziis SeCerebis aucileblobas da iolad kupirebadia analgetikebis an sicxisdamwevi saSualebebis gamoyenebiT – paracetamoli an antihistaminuri preparatebi, magaliTad difenhidramini. sxva simtomebi SeiZleba iyos gulisreva, Rebineba, tkivili, tremori, Tavis tkivili, Tavbrsxveva, qoSini, hipotonia, gamonayari da asTenia. herceptinis ganmeorebiTi infuziebisas es simptomebi iSviaTad vlindeba.

hipermgrZnobelobis reaqciebi: calkeul (erTeul) SemTxvevebSi aRiniSna anafilaqtoiduri reaqciebi.

kardiotoqsiuroba: preparatiT monoTerapiisas gulis zomieri da mZime ukmarisobis (NYHA III/IV klasi) sixSirem Seadgina 5%. hematologiuri toqsikuroba: herceptiniT monoTerapiisas hematotoqsikuroba iSviaTad viTardeba. me-3 xarisxis leikopenia janmos klasifikaciis mixedviT, Trombocitopenia da anemia aRiniSneba pacientebis 1%-ze naklebSi. me-4 xarisxis toqsiurobis niSnebi ar aRniSnula.

hepatologiuri toqsiuroba: herceptiniT monoTerapiisas me-3 da me-4 xarisxis hepatotoqsiuroba janmos klasifikaciiT aRiniSna avadmyofebis 12%-Si. maTgan 60%-Si hepatotoqsiurobis movlenebi ganviTarda RviZlis metastazuri dazianebis progresirebis fonze. me-3 da me-4 xarisxi nefrotoqsiuroba ar aRniSnula. diarea: herceptiniT monoTerapiisas diarea aRiniSna pacientebis 27%-Si.

RviZlis da Tirkmlis toqsikuroba

WHO-s III an IV klasis RviZlis toqsikuroba aReniSna pacientebis 12%-s, herceptinis calke miRebisas. aseT pacientTa 60%-Si, es toqsikuroba dakavSirebuli iyo RviZlis daavadebis progresirebasTan

WHO-s III an IV klasis RviZlis toqsikuroba ufro naklebi sixSiriT gamovlinda im pacientebSi, romlebic herceptins Rebulobdnen paklitaqselTan erTad, im pacientebTan SedarebiT, romlebic mxolod paklitaqsels Rebulobdnen (7% da 15%, Sesabamisad).

diarea

herceptinis monoTerapiis qveS myof pacientTa 27%-s aReniSna diarea, msubuqidan saSualomde simwvavis formiT diarea momatebuli sixSiriT aReniSna  im pacientebs, romlebic herceptins Rebulobdnen paklitaqselTan erTad, im pacientebTan SedarebiT, romlebic m