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samedicino gamoyenebis instruqcia

selsepti

CellCept mikofenolatis mofetili 1. aRwera 1.1 preparatis Terapevtuli /farmakologiuri klasi imunosupresori; inozin monofosfat dehidrogenazas (IMPDH) inhibitori. 1.2 dozirebis formis saxeebi oraluri miReba: selsepti iwarmoeba rogorc kafsulebSi, aseve tabletebSi. intravenuri miReba: selsepti iwarmoeba erTjeradad gamosayenebel ampulaSi rogorc fxvnili sainieqcio xsnarisaTvis. 1.3. miReba kafsulebi da tabletebi miiReba oralurad. Ampulebis SigTavsi - intravenurad. 1.4. xarisxobrivi da raodenobrivi Semadgenloba aqtiuri ingredienti: mikofenolat mofetili (MMF). oraluri miReba: TiToeuli kafsula Seicavs 250 mg mikofenolat mofetils; TiToeuli tableti Seicavs 500 mg mikofenolat mofetils. intravenuri miReba: TiToeuli ampula aris 500 mg mikofenolat mofetilis eqvivalenti (rogorc hidroqloridis marili). 2. klinikuri maxasiaTeblebi 2.1. Terapeiuli daniSnuleba selsepti iniSneba organos mwvave miuReblobis/mocilebis profilaqtikisaTvis da pirveladi gadanergvisas an organos mocilebisas (ukugdebisas) im pacientebSi, romlebsac gaaCniaT Tirkmlis alogenuri gadanergva. selsepti gamoiyeneba organos mwvave miuReblobis profilaqtikisaTvis pacientebSi, romlebsac gaaCniaT gulis alogenuri gadanergva. mkurnal mosaxleobaSi, MMF-is meSveobiT gaumjobesda sicocxlisunarianoba gadanergvis Semdeg pirveli wlis ganmavlobaSi. selsepti gamoiyeneba organos mwvave miuReblobis /mocilebis profilaqtikisaTvis pacientebSi, romlebsac gaaCniaT RviZlis alogenuri gadanergva. selsepti unda gamoiyenebodes erTdroulad ciklosporinTan da kortikosteroidebTan erTad.

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2.2. dozireba da miRebis wesi standartuli dozireba profilaqtikisaTvis Tirkmlis gadanergvisas mocilebisas doza 1 gramis odenobiT miiReba oralurad an intravenurad (aranakleb 2

saaTis ganmavlobaSi) orjer dReSi (dRiuri doza – 2 grami) rekomendebulia pacientebSi, romlebsac gaaCniaT Tirkmlis gadanergva. Tumca 1.5 grami doza miiReboda orjer dReSi (dRiuri doza 3 grami) klinikuri cdebis dros da gamovlinda, rogorc usafrTxo da efeqturi, ar gamovlinda aranairi efeqturobis upiratesoba pacientebSi, romlebsac gaaCndaT Tirkmlis gadanergva. pacientebs, romlebic Rebulobdnen selseptis 2 grams/dReSi aRmoaCndaT ukeTesi saerTo mdgomareoba im pacientebTan SedarebiT, romlebic Rebulobdnen selseptis 3 grams/dReSi. standartuli dozireba profilaqtikisaTvis gulis gadanergvisas mocilebisas doza 1.5 gramis odenobiT miiReba oralurad an intravenurad (aranakleb

2 saaTis ganmavlobaSi) orjer dReSi (dRiuri doza – 3 grami) rekomendebulia pacientebSi, romlebsac gaaCniaT gulis gadanergva. standartuli dozireba profilaqtikisaTvis RviZlis gadanergvisas mocilebisas doza 1 gramis odenobiT miiReba oralurad an intravenurad (aranakleb 2

saaTis ganmavlobaSi) orjer dReSi (dRiuri doza – 2 grami) an 1.5 grami oralurad orjer dReSi (dRiuri doza 3 grami) rekomendebulia pacientebSi, romlebsac gaaCniaT RviZlis gadanergva. standartuli dozireba profilaqtikisaTvis RviZlis mwvave micilebis profilaqtikisaTvis da pirveladi an refraqtoruli mocilebisas doza 1.5 gramis odenobiT miiReba oralurad an intravenurad (aranakleb

2 saaTis ganmavlobaSi) orjer dReSi (dRiuri doza – 3 grami) rekomendebulia pirveladi an refraqtoruli mocilebisas samkurnalod. oraluri miReba (ix. 3.2.5. bioeqvivalenturoba) selseptis pirveladi doza unda miRebul iqnas rac SeiZleba swrafad Tirkmlis, gulis an RviZlis gadanergvis Semdeg. intravenuri miReba selsepti intravenuri aris alternatiuli doza selseptis kafsulebisa da tabletebisa, romelic rekomendebulia pacientebisaTvis, romlebic ver Rebuloben selsepts oralurad. selsepti intravenuri unda miRebul iqnas 24 saaTis ganmavlobaSi gadanergvidan. selsepti intravenuri SeiZleba miiRebodes 14 dRis ganmavlobaSi. pacientebi unda gadayvanil iqnan oralur selseptze rac SeiZleba droulad, rogorc ki eqnebaT wamlis oralurad miRebis amtanoba. 5%-iani deqstrozis intravenuri xsnaris gazavebis da gaxsnis Semdeg 6 mg/ml koncentraciamde, selsepti intravenuri unda Seyvanil iqnas neli infuziiT periodSi, romelic ar unda Seadgendes 2 saaTze naklebs periferiuli an centraluri venidan.

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2.2.1 specialuri dozirebis instruqcia pacientebi neitropeniiT im SemTxvevaSi Tu neitropenia viTardeba (absoluturi neitropiuli maCvenebeli <1.3X103/ml), selseptis dozireba unda SeCerdes an doza Semcirdes (ix. 2.4 gafrTxileba da sifrTxilis zomebi da 2.4.1 zogadi). dozirebis instruqciisaTvis garkveul SemTxvevebSi/mosaxleobaSi, Tu SeiZleba ixileT seqciebi 2.5.3 – geriatriuli gamoyeneba, 2.5.4 Tirkmlis daqveiTeba da 2.5.5 RviZlis daqveiTeba. 2.3. ukuCvenebebi SeniSnulia alergiuli reaqciebi selseptis mimarT. amgvarad, selseptis miReba dauSvebelia mikofenolatis mofetilis an mikofenoliuri mJavis (MPA) mimarT hipermgrZnobiare pacientebisaTvis. selsepti intravenuri aseve dauSvebelia misaRebad pacientebisaTvis, romlebsac gaaCniaT hipermgrZnobeloba polisorbiti 80-is mimarT. 2.4. gafrTxileba da sifrTxilis zomebi 2.4.1. zogadi vinaidan yvela pacienti, romelic Rebulobs imunosupresors wamlebis kombinirebiT, pacientebi, romlebic Rebuloben selsepts, rogorc imunosupresiis reJimis nawils, arian limfomis da sxva avTvisebiani warmonaqmnebis ganviTarebis riskis qveS, gansakuTrebiT kanis (ix. 2.6 arasasurveli efeqtebi). riski, rogorc Cans, dakavSirebulia imunosupresiis intensiurobasa da xangrZlivobasTan ufro, vidre sxva raime specifiuri agentis miRebasTan. amgvarad, yvela pacienti, romelsac gaaCnia kanis kibos maRali riski, unda moeridon mzes da ultraiisfer sxivebs damcavi tansacmlis meSveobiT da mzisgan damcavi maRali faqtoriani kremis saSualebiT. pacientebi, romlebic Rebuloben selsepts unda informirebulni iyvnen, rom aucileblad unda Seatyobinon nebismieri infeqciis Taobaze, moulodneli dalurjebebis warmoqmnaze, sisxldenaze an Zvlis tvinis dazianebis nebismier sxva gamoxatulebaze. imunuri sistemis zesupresias/daTrgunvas SeuZlia gazardos mgrZnobeloba infeqciebis mimarT oportunistuli infeqciebis, sasikvdilo infeqciebisa da sefsisis CaTvliT (ix. 2.6. arasasurveli efeqtebi). msgavs infeqciur garTulebebSi moazreba latenturi virusebis reqtivacia, rogorebicaa hepatiti B-s an hepatiti C-s vurisebis reaqtivacia, an poliomavirusuli infeqciebi. hepatiti B-s da hepatiti C-s vurisebis matareblebSi aRwerilia reqtivaciis SemTxvevebi ganviTarebuli imunosupresorebiT mkurnalobisas fonze. selseptiT namkurnaleb pacientebSi aRwerilia JC

virusTan asocirebuli progresuli multifokaluri leikoencefalopaTiis (pml) SemTxvevebi, romelTac zogjer fataluri gamosavalic ki hqonda.

imunosupresiis mqone pacientebის mkurnalobis dros, Tuki pacintebs gamouvlindebaT nevrologiuri simptomebi, eqimebma unda gaiTvaliswinon pml diferencialuri diagnozis gatarebisas da klinikuri mdgomareobis mixedviT mimarTon nevrologis konsultacias.

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Tirkmel-gadanergili pacientebis selseptiT mkurnalobis dros aRwerilia bk-virusTan asocirebuli nefropaTiis SemTxevevebi. es aris seriozuli infeqciuri garTuleba, romelmac SeiZleba gamoiwvios gadanergili organos dazianeba. bk-virusTan asocirebuli nefropaTiis riskis dasadgenad saWiroa aseTi pacientebis monitoringi. bk-virusTan asocirebuli nefropaTiis riskis mqone pacientebSi naCvenebia imunosupresiuli Terapiis Semcireba.

selseptiT sxva imunosupresorebTan kombinaciaSi mkurnalobis dros SesaZlebelia ganviTardes wiTeli ujredebis WeSmariti aplazia. mikofenolatis mofetiliT inducirebuli wiTeli ujredebis WeSmariti aplaziis ganviTarebis meqanizmi ucnobia, aseve ucnobia sxva imunosupresorebis an imunosupresorebis kombinirebuli gamoyenebis wvlili aplaziis ganviTarebaSi. zogierT SemTxvevaSi, selseptis dozis Semcirebis an mkurnalobis Sewyvetis Semdeg wiTeli ujredebis WeSmariti aplazia ganicdida ukuganviTarebas. Tumca, organogadanergil pacientebSi imunosupresiuli Terapiis Semcireba SeiZleba dakavSirebuli iyos transplantatis dazianebis riskTan.

gafrTxileba: selsepti intravenuri xsnari arasoder ar unda miiRebodes

swrafi an bolusuri intravenuri inieqciis saxiT. pacientebs unda ecnobos, rom selseptiT mkurnalobisas vaqcinacia SeiZleba iyos naklebefeqturi da janmrTelobis damasustebel vaqcinebs unda moeridon (ix. 2.4.2 urTierTqmedeba sxva samedicino produqtebTan da urTierTqmedebis sxva formebi). influencas vaqcinacia SeiZleba iyos mizanSewonili. eqimma, romelic daniSnavs wamals, unda ixelmZRvanelos influencis vaqcinaciis erovnuli instruqciiT. vinaidan selsepti dakavSirebulia saWmlis momnelebeli sistemis sawinaaRmdego efeqtebis xSir SemTxvevebTan, kuWnawlavis traqtis dawylulebis iSviaTi SemTxvevebiT, sisxldenasTan da xvretasTan/perforaciasTan, selsepti unda dainiSnos yuradRebiT pacientebSi saWmlis momnelebeli sistemis aqtiuri daavadebiT. vinaidan selsepti aris inozin monofosfatis dehidrogenazis (IMPDH) inhibitori, Teoriulad is unda aaridon pacientebisaTvis iSviaTi memkvidreobiTi hipoqsantin-guanin fosforibosil-transferazis ukmarisobiT (HGPRT) rogoricaa leS-niani (Lesch-Nyhan) da keli-sigmileris (Kelley-Seegmiller) sindromi. rekomendebulia, selsepti ar iqnas gamoyenebuli erTdorulad azaTiorpinTan, radgan orives SeuZlia gamoiwvios Zvlis tvinis supresia da amgvari erTdrouli miReba ar aris Seswavlili. rac Seexeba qolestiraminis mier MPA-s AUC-iT mniSvnelovan Semcirebas, yuradRebiT unda iqnas miRebuli selsepti erTdroulad im wamlebTan, romlebic urTierTqmedeben enTeropatiul recirkulaciasTan, maTi SesaZleblobis gamo, Seamciron selseptis efeqturoba (ix. 2.4.2 urTerTqmedeba sxva samedicinoi produqtebTan da urTierTqmedebis sxva formebi).

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1 gramze meti dozireba orjer dReSi (b.i.d) pacientebSi mwvave qronikuli Tirkmlis mocilebiT unda iqnas acilebuli Tavidan (ix. 3.2 farmakokinetikuri maxasiaTeblebi da 2.2.1 specialuri dozirebis instruqcia). ar aris rekomendebuli dozis koreqtireba pacientebSi post-gadanergviT, Tirkmlis dayovnebuli gadanergvis fuqnciiT, magram pacientebi unda iyvnen dakvirvebis qveS (ix. 3.2 farmakokinetikuri maxasiaTeblebi da 2.2.1 specialuri dozirebis instruqcia). ar aris informacia pacientebze gulis an RviZlis gadanergviT Tirkmlis mwvave daqveiTebiT. asakovani/moxuci pacientebi arian ukuCvenebiTi efeqtebis riskis qveS, axalgazrdebTan SedarebiT (ix. 2.6 arasasurveli efeqtebi). laboratoriuli dakvirveba selseptis mimRebma pacientebma yovelkvireulad unda Caabaron sisxlis analizi mkurnalobis pirveli Tvis ganmavlobaSi, orjer TveSi meore da mesame Tves, Semdgom ki yovelTviurad pirveli wlis ganmavlobaSi. kerZod, pacientebi, romlebic Rebuloben selsepts, unda Semowmdnen neitropeniaze. neitropeniis ganviTareba SeiZleba dakavSirebuli iyos selseptTan, erTdroulad (paralelurad) miRebul medikamentebTan, virusul infeqciebTan an am mizezebis raime kombinaciasTan (ix. 2.2.1 specialuri dozirebis instruqcia). im SemTxvevaSi, Tuki neitropenia viTardeba (absoluturi neitropiuli maCvenebeli <1.3X 103/µl) selseptis dozireba unda Sewydes an doza Semcirdes da pacients unda Cautardes gamokvleva (ix. 2.2.1 specialuri dozirebis instruqcia). 2.4.2 urTierTqmedeba sxva samedicino produqtebTan da urTierTqmedebis sxva formebi acikloviri: ufro maRali MPAG (MPA-s fenoliuri glukoronidi) da acikloviruli plazmis koncentracia SemCneul iqna mikofenolat mofetilis miRebisas aciklovirTan erTad da ara wamlebis cal-calke miRebisas. vinaidan MPAG plazmis koncentracia matulobs Tirkmlis daqveiTebisas, rogoricaa acikloviris koncentraciebi, arsebobs SesaZlebloba mikofenolatma da aciklovirma an maTgan warmoebulma wamlebma, magaliTad, valaciklovirma gamoiwvios milovani sekrecia, orive wamlis koncentraciis gazrdiT. antacidebi da protonuli pompis inhibitorebi: mikofenolis mJavis eqspozicia mcirdeba, rodesac selsepti miiReba antacidebTan (rogorebbicaa magneziis da luminis hidroqsidebi) da protonuli pompis inhibitorebTan (lansoprazoli da pantoprazoli) erTad. transplantantis dazianebis an transplantantis mocilebis reaqciis sixSireebSi mniSvnelovani gansxvavebebi ar iqna nanaxi pacintebSi, romlebic iRebdnen selsepts protonuli pompis inhibotorebTan erTad, im pacinetebTan SedarebiT, romlebic iRebdnen mxolod selsepts protonuli pompis inhibotorebis gareSe. es monacemebi SeiZleba mivusadagoT yvela antacids, vinaidan selseptis eqspoziciis Semcireba bevrad naklebi iyo selseptis da

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antacidebis erTdrouli daniSvnis dros selseptis da protonuli pompis inhibitorebis kombinaciasTan SedarebiT. qolestiramini: mikofenolat mofetilis 1.5 g erTjeradi dozis miRebiT normalur janmrTel winaswar namkurnaleb subieqtebSi qolestiraminis 4 dRis ganmavlobaSi 4 gramis 3-jer dReSi (t.i.d.) miRebiT, gamoCnda MPA-s AUC-iT 40% Semcireba. yuradReba unda mieqces erTdroulad miRebisas an wamlebTan, romlebic urTierTqmedeben enTeropatiul cirkulirebasTan (ix. 2.4 gafrtxileba da sifrTxilis zomebi). ciklosporini A: ciklosporini A (CsA)–s farmakokinetikaze ar moaxdina gavlena mikofenolat mofetilma. mainc pacientebSi Tirkmlis gadanergviT selseptis da CsA-s erTdroulma miRebam gamoiwvia mikofenolis mJavis gamovlenis Semcireba 30-50%-iT im pacientebTan SedarebiT, romlebic Rebulobdnen sirolimusis kombinacias da selseptis igive odenobis dozebs. gancikloviri: oraluri mikofenolatis da intravenuri gancikloviris rekomendebuli dozebis Seswavlis safuZvelze erTjeradi dozis miRebisas da MMF-is da gancikloviris farmakokinetikaze Tirkmlis daqveiTebis cnobili efeqtebis safuZvelze (ix. 3.2 farmakokinetikuri maxasiaTeblebi da 2.4 gafrTxileba da sifrTxilis zomebi) mosalodnelia, rom am agentebis erTdrouli miRebiT (romlebic pasuxismgebelia Tirkmlis milovan sekreciaze) miiReba Sedegi MPAG-s matebaSi da gancikloviris koncentraciaSi. ar aris mosalodneli MPA-s farmakokinetikis arsebiTi cvlileba da ar aris saWiro MMF dozis koreqtireba. pacientebSi Tirkmlis daqveiTebiT, rodesac MMF da gancikloviri aris misgan warmoebuli wamlebi, magaliTad valgancikloviri da miiReba erTdroulad, pacientebi unda iyvnen dakvirvebis qveS. oraluri kontraceptivebi: oraluri kontraceptivebis farmakokinetikaze ar axdens gavlenas selseptis erTdrouli miReba. selseptis erTdrouli miRebis gamokvlevisas (1 grami dReSi orjer b.i.d.) da kombinirebulad oraluri kontraceptivebi, romlebic Seicavs eTinilestradiols (0.02-0.04 mg) da levonorgestrels (0.05-0.20 mg), dezogestrels (0.15 mg) an gestodins (0.05-0.10 mg), romelic Cautarda 18 qalbatons fsoriaziT 3-ze meti menstrualuri ciklis dros, ar aCvena selsptis klinikuri gavlena

progesteronis Sratis doneze, LH da FSH, amgvarad ar aCvena selseptis raime gavlena oraluri kontraceptivebis ovulaciis Seferxebis qmedebaze (ix. 2.5.1 orsuloba). rifampicini: dozis koreqtirebis Semdeg MPA –Si gamovlinda 70% Semcireba (AUCO-12h) rifampicinis erTdrouli miRebiT pacientSi gulis parkuWis gadanergviT. amgvarad rekomendebulia dakvirveba MPA –s gamovlinebis doneze da selseptis dozis koreqtireba Sesabamisad klinikuri efeqturobis SesanarCuneblad wamlebis erTdrouli miRebisas. takrolimusi: selseptTan erTad takrolimusis erTdrouli miRebisas ar gaaCnda gavlena AUC–ze an Cmax-s MPA–ze pacientebSi RviZlis gadanergviT. igive dakvirvebul iqna ukanasknel dros pacientebSi Tirkmlis gadanergviT. pacientebSi Tirkmlis gadanergviT ar gamovlinda takrolimusis koncentraciis cvlileba selseptis gavleniT.

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amrigad, stabilur pacientebSi RviZlis gadanergviT, ar iyo SemCneuli daaxloebiT 20% takrolimusis AUC zrda selseptis mravaljeradi dozis miRebisas (1.5 grami orjer dReSi) pacientebisaTvis, romlebic Rebulobdnen takrolimuss. ciprofloqsacini da amoqsicilini plus klavulinis mJava: Tirkmelgadanergil pacientebSi ciprofloqsaciniT da amoqsicilini plus klavulinis mJaviT peroraluri Terapiis pirvelive dReebSi aRiniSneba mikofenolis mJavis predozis koncentraciis 54%-iT Semcireba. es efeqti mcirdeba Semdegi dReebis ganmavlobaSi da qreba am antibitikebiT mkurnalobis Sewyvetis Semdeg. es monacemebi maincdamainc zustad ar asaxavs mTlianad mikofenolis mJavis eqspozicias, amitom am monacemebis klinikuri mniSvneloba gaurkvevelia. trimeToprimi/sulfametoqsazoli, norfloqsacini da metronidazoli: ar aris SemCneuli MPA-s sistemur gamovlinebaze gavlena selseptis erTdrouli miRebiT nebismier antibiotikTan cal-calke. amis sawinaaRmdegod, norfloqsacinis da metronidazolis kombinirebam Semcira MPA AUC0-48 30%-iT selseptis erTjeradi dozis miRebis Semdeg. sxva urTierTqmedeba: probenecidis mikofenolat mofetilTan erTad erTdroulma miRebam maimunebSi gazarda MPAG-is AUC-is plazma 3-jer. amrigad, sxva wamlebi, romelic cnobilia, rom ganicdian Tirkmlis tubularul (milovan) sekrecias, SeiZleba Seedaron MPAGs da amgvarad gazardon MPAG-s an im sxva wamlis plazmis koncentracia, romelic ganicdis tubularul sekrecias. sevelameris da selseptis erTdroulma miRebam zrdasrulebSi da pediatriul pacientebSi Seamcira MPA Cmax da AUC0-12 30%-iT da 25%-iT Sesabamisad. es informacia gulisxmobs, rom sevelameri da ukalcio fosfatis narevi arCeviT unda mieces 2 saaTis Semdeg selseptis miRebidan

MPA-s Sewovis gavlenis minimizirebisaTvis. sasicocxlo vaqcinebi: sasicocxlo vaqcinebi ar unda Cautardes pacientebs daqveiTebuli imunuri SesaZleblobiT. antisxeulebis Sedegi sxva vaqcinebze SeiZleba Semcirdes (ix. 2.4 gafrtxileba da sifrTxilis zomebi). 2.5. gamoyeneba gansakuTrebul SemTxvevebSi (mosaxleobaSi) 2.5.1. orsuloba C kategoriis orsuloba nayofis ganviTarebaze (simaxinjeebis CaTvliT) gverdiTi movlenebi SemCneuli iyo, rodesac orsul virTxebs da bocverebs miecaT wamali organogenezisis dros. amgvar SemTxvevebs hqonda adgili im dozebis miRebisas, romelic ufro naklebia, dediseuli mowamvlisaTvis, da im dozebis, romelic ufro mcirea rekomendebul klinikur dozaze Tirkmlis, gulis an RviZlis gadanergvisas. ar aris Catarebuli adeqvaturi da kargad kontrolirebadi Seswavla orsul qalebze. amrigad, selsepti gamovlinda, rogorc teratogeniuli gavlenis mqone cxovelebze, mas SeuZlia daazianos nayofi, rodesac miiReba orsuli qalis mier. amgvarad, selseptis miRebas unda aaridon Tavi orsulma qalebma garda im SemTxvevebisa, rodesac SesaZlo Sedegi ufro mniSvnelovania, vidre Canasaxis riski.

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qalebs fexmZimobis periodSi unda gaaCndeT negatiuri Srati an Sardis

orsulobis tests unda gaaCndes mgrZnobeloba aranakleb 50mIU/ml Terapiis dawyebamde 1 kviriT adre. rekomendebulia, rom selseptis Terapia ar unda iqnas wamowyebuli eqimis mier, sanam ar miiReba daskvna negatiuri fexmZimobis Sesaxeb. selseptiT mkurnalobamde unda gamoiyenebodes efeqturi kontracefcia, aseve mkurnalobisas da mkurnalobis dasrulebidan 6 kviris ganmavlobaSi, im SemTxvevaSic ki, rodesac pacients gaaCnia uSvilobis istoria, Tuki is ar aris gamowveuli histerektomiiT. unda gamoiyenebodes kontracefciis 2 sando forma, Tuki SerCeuli periodi ar aris TavSekavebis periodi (ix. 2.4.2 urTierTqmedeba sxva samedicino produqtebTan da urTierTqmedebis sxva formebi). im SemTxvevaSi, Tu pacienti daorsuldeba mkurnalobis dros, eqimi da pacienti unda SeTanxmdnen orsulobis gagrZelebis sasurvelobaze. 2.5.2 meZuZuri dedebi virTxebSi Seswavlam gamoavlina mikofenolat mofetilis gamoyofa rZeSi. ar aris cnobili gamoiyofa Tu ara wamali adamianis rZeSi. vinaidan mravali preparati gamoiyofa rZeSi, CvilebSi seriozuli gverdiTi movlenebis SesaZleblobis gamo mikofenolat mofetilisagan, unda gadawyvetil iqnas, gagrZeldes Tu ara kveba Tu gagrZeldes Tu ara wamlis miReba, dedisaTvis wamlis miRebis mniSvnelobidan gamomdinare. 2.5.3 geriatriuli gamoyeneba rekomendebuli oraluri dozaa 1 grami dReSi orjer pacientebSi Tirkmlis gadanergviT da 1.5. grami dReSi orjer pacientebSi gulis an RviZlis gadanergviT, Sesabamisia zrdasruli pacientebisaTvis (ix. 2.4. gafrTxileba da da winaswari zomebi). 2.5.4 Tirkmlis funqciis daqveiTeba pacientebi Tirkmlis mwvave daqveiTebiT pacientebSi Tirkmlis gadanergviT Tirkmlis mwvave qronikuli daqveiTebiT (glomerularuli filtraciis maCvenebeli <25ml/min/1.73 m2) uSualod post-gadanergvis periodidan an mkurnalobis Semdeg mwvave an refraqtoruli mocilebisas, unda Tavidan iqnas acilebuli dozis miReba 1 gramze meti orjer dReSi (ix. 2.4 gafrTxileba da sifrTxilis zomebi). ar aris informacia gulis an RviZlis gadanergvis mqone pacientebSi Tirkmlis mwvave qronikul daqveiTebaze. pacientebi Tirkmlis gadavadebuli gadanergvis graftuli funqciiT gadanergvis Semdeg ar aris saWiro dozis koreqtireba pacientebSi, romlebsac gaaCniaT gadavadebuli gadanergvis graftuli funqcia gadanergvis Semdeg (ix. 3.2 farmakokinetikuri maxasiaTeblebi).

9

2.5.5. RviZlis funqciis daqveiTeba ar aris saWiro dozis koreqtireba pacientebSi RviZlis mwvave parenqimaluri daavadebiT (ix. 3.2 farmakokinetikuri maxasiaTeblebi). ar aris informacia gulis an RviZlis gadanergvis mqone pacientebisaTvis mwvave parenqimaluri daavadebiT. 2.6. arasasurveli movlenebi arasasurveli movlenebi dakavSirebulia imunosupresor wamlebTan da zogjer Znelia maTi dadgena sxva arsebuli Tanmxlebi daavadebebis gamo da sxva wamlebis Tanadrouli mimdinare miRebis gamo. 2.6.1 klinikuri kvlevebi ZiriTadi gverdiTi movlenebi asocirebuli selseptis miRebasTan Tirkmlis, gulis da RviZlis gadanergvisas, mocilebis Tavidan asacileblad ciklosporinis da kortikosteroidebis kombinirebiT. eseni aris diarea, leikopenia, sefsisi da Rebineba; dadasturebulia infeqciis garkveuli tipebis maRali sixSire, magaliTad oportunistuli infeqciebi (ix. 2.4 gafrTxileba da sifrTxilis zomebi). gverduTi movlenebi dakavSirebulia selseptis miRebasTan intravenurad, romelic msgavsia misi oraluri miRebis Sedegis. selseptis usafrTxoeba Tirkmel-gadanergil pacientebSi, romlebsac mkurnaloben transplantantis refraqtoruli mocilebis reaqciis gamo, iyo msgavsi imisa, rac gamovlinda sami kontrolirebadi kvlevis dros, rodesac mkurnalobdnen doziT 3 grami dReSi. diarea da leikopenia, romelTac Tan sdevda anemia, gulisreva, tkivili muclis areSi, sefsisi, Rebineba da dispepsia, iyo ZiriTadi gverdiTi movlenebi, romelic daafiqsires pacientebma, romlebic Rebulobdnen selsepts im pacientebTan SedarebiT, romlebic Rebulobdnen kortikosteroidebs intravenurad. avTvisebianoba vinaidan pacientebSi, romlebic Rebuloben imunosupresorebs wamlebis kombinaciebis CaTvliT, pacientebi, romlebic Rebuloben selsepts, rogorc imunosupresoruli reJimis nawils, arian limfomebis da sxva avTvisebiani warmonaqmnebis ganviTarebis riskis qveS, gansakuTrebiT maTi kani (ix.2.4 gafrTxileba da sifrTxilis zomebi da 2.4.1.zogadi). limfoproliferatiuli daavadeba anu limfoma ganviTarda 0.4%-dan 1% pacientebSi, romlebic Rebulobdnen selsepts (2 grami an 3 grami dReSi) sxva imunosupresantebTan kombinaciaSi, kontrolirebadi klinikuri testirebisas Tirkmlis, gulis da RviZlis gadanergvisas pacientebSi, minimum 1 wlis ganmavlobaSi. Aara melanomiani kanis karcinomis SemTxveva iyo 1.6% dan 3.2.%-mde pacientebSi; sxva avTvisebianobis SemTxvevebi iyo 0.7%-dan 2.1% pacientebSi. sami wlis usafrTxoebis informaciam Tirkmlis da gulis gadanergil pacientebSi ar gamoavlina raime moulodneli cvlilebebi avTvisebianobis SemTxveviTobaSi, 1 wlis informaciasTan SedarebiT. pacientebSi RviZlis gadanergviT dakvirveba mimdinareobda minimum 1 wlis ganmavlobaSi, magram 3 weliwadze nakleb dros. Tirkmlis refraqtoruli mocilebis mkurnalobis kontrolirebad kvlevebSi limfomis done iyo 3.9% saSualo midevnebiT 42 Tvemde.

10

oportunistuli infeqciebi yvela pacienti gadanergviT aris oportunistuli infeqciebis riskis qveS. riski izrdeba mTliani imunosupresoruli efeqtis gamo (ix. 2.4 gafrTxileba da sifrTxilis zomebi). yvelaze xSiri oportunistuli infeqciebi dakvirvebulia pacientebSi, romlebic Rebuloben selsepts (2 grami an 3 grami dReSi) sxva imunosupresantebTan erTad kontrolirebadi klinikuri dakvirvebisas pacientebSi Tirkmlis (2 grami informaciiT), gulis da RviZlis gadanergviT periodSi dakvirvebiT aranekleb 1 wlisa, rac iyo kandida mukokutaneosi, CMV viremia/sindromi da Cveulebrivi herpesi. pacientebis Sefardeba CMV /viremia sindromiT iyo 13.5%. xandazmuli pacientebi (≥65 wlis) xandazmuli pacientebi, gansakuTrebiT isini, romlebic Rebuloben selsepts, rogorc imunosupresoruli reJimis nawils, SeiZleba iyvnen garkveuli infeqciebis (citomegalovirusis qsovilis Semtevi daavadebis CaTvliT) da SesaZlebeli kuW-nawlavis sisxldenis da pulmonaruli edemis ufro maRali riskis qveS, vidre axalgazrdebi (ix. 2.4 gafrTxileba da sifrTxilis zomebi da 2.4.1.zogadi).). selspetis usafrTxoeba oraluri miRebisas gverdiTi movlenebi iyo ≥10% da 3-<10% im pacientebSi, romlebsac mkurnalobdnen selspetiT kontrolirebad cdebSi Tirkmlis gadanergvis mocilebisas (3 cda, 2 grami da 3 grami) erTi kontrolirebadi gulis gadanergvis cda da erTi kontrolirebadi RviZlis gadanergvis cda mocemulia cxrilSi qvemoT. selseptis usafrTxoeba intravenuri miRebisas gverdiTi movlenebi selseptis intravenuri miRebisas igivea, rac oraluri miRebisas. gverdiTi movlenebi dakavSirebuli periferiul venur infuziasTan iyo flebiti da Trombozi, orive dakvirvebuli selseptis intravenurad mimReb 4% pacientebSi. gverdiTi movlenebi SemCneuli ≥10% da 3-<10% pacientebSi, romlebsac mkurnalobdnen selseptiT klinikuri cdebisas zrdasrulebSi, rodesac is gamoiyeneboda ciklosporinTan da kortikosteroidebTan kombinaciaSi.

sxeulis sistema gverdiTi movlenebi pacientebSi Tirkmlis

gadanergviT (n=991)*

gverdiTi movlenebi pacientebSi

gulis gadanergviT

(n=289)**

gverdiTi movlenebi pacientebSi RviZlis

gadanergviT (n=277)***

sxeuli mTlianobaSi

≥10% asTenia, cieba, Tavis tkivili, infeqcia, tkivili (moicavs muclis, zurgis da mkerdis), edema, sefsisi

asTenia, cieba, Secieba, Tavis tkivili, infeqcia, tkivili (moicavs muclis, zurgis da mkerdis) edema, sefsisi

ascitebi, asTenia, Secieba, gamoberili muceli, cieba, Tavis tkivili, Tiaqari, infeqcia, tkivili (moicavs

11

muclis, zurgis da mkerdis), edema, peritoniti, sefsisi

3- <10% kista (moicavs limfocele da hidrocele), gamoberili muceli, saxis edema, gaciebis sindromi, sisxldena, Tiaqari, uZlureba, menjis tkivili

celuliti, kista (moicavs limfocele da hidrocele), gamoberili muceli, saxis edema, gaciebis sindromi, sisxldena, Tiaqari, uZlureba, kisris tkivili, palori, menjis tkivili

abscesi, celuliti, kista (moicavs limfocele da hidrocele), gaciebis sindromi, sisxldena, uZlureba, kisris tkivili

sisxlis da limfaturi

≥10% anemia (hipoqromuli anemiis CaTvliT), leikocitozi, leikopenia, Trombocitopenia

anemia (hipoqromuli anemiis CaTvliT), eqximozisi, leikocitozi, leikopenia, Trombocitopenia

anemia (hipoqromuli anemiis CaTvliT), leikocitozi, leikopenia, Trombocitopenia

3- <10% eqximozisi, policitemia

peteqia, proTrombinis drois momateba, Tromboplastinis drois momateba

eqximozisi, mancitopenia, proTrombinis drois momateba

urogenitaluri ≥10% hematuria, Tirkmlis tubularuli nekrozi, Sardis traqtis infeqcia

Tirkmlis abnormaluri funqcia (Tirkmlis funqciis Semcireba, Sratis momatebuli kreatinini), oliguria, Sardis traqtis infeqcia

Tirkmlis abnormaluri funqcia (Tirkmlis funqciis Semcireba, Sratis momatebuli kreatinini), oliguria, Sardis traqtis infeqcia

3- <10% albuminuria, dizuria, hidronefrozi, impotencia, pielonefriti, Sardis gamoyofis sixSire

dizuria, hematuria, impotencia, nokturia, Tirkmlis moqmedebis daqveiTeba, Sardis gamoyofis sixSire, Sardis Seukavebloba, SardSekaveba

Tirkmlis funqciis moqmedebis mwvave daqveiTeba, dizuria, hematuria, Tirkmlis fuqnciis daqveiTeba, skrotaluri edema, Sardgamoyofis sixSire, Sardis Seukavebloba

12

sxeulis sistema gverdiTi

movlenebi pacientebSi Tirkmlis



gulis gadanergviT

(n=289)**

gverdiTi movlenebi pacientebSi RviZlis gadanergviT (n=277)***

kardio vaskularuli

≥10% maRali arTerialuri wneva

ariTmia, bradikardia, gulis funqciis SeCereba, maRali arTerialuri wneva, dabali wneva, perikardiuli efuzia

maRali arTerialuri wneva, dabali wneva, taqikardia

3-<10% angina pektorisi, atrialuri fibrilacia, dabali arTerialuri wneva, postularuli dabali wneva, taqikardia, Trombozi, sisxlZarRvebis dilatacia

angina peqtorisi, ariTmia (supraventrikularulis da ventrikularuli eqstrasistolis CaTvliT, atrialuri fluteri, supraventrikularuli da ventrikularuli taqikardia), atriuli fibrilacia, gulis gaCereba, gulis moqmedebis SeCereba, posturaluri dabali wneva, pulmonaruli maRali wneva, sinkopi, sisxlZarRvebis spazmi, venebis maRali wneva

arteriuli Trombozi, atrialuri fibrilacia, ariTmia, bradikardia, sisxlZarRvebis dilatacia, sinkopi

metabolikuri/sakvebi

≥10% hiperqolesterolemia, hiperglikemia, hiperkalemia, hipokalemia, hipofosfatemia

acidozi (metabolikuri an respiratoruli), bilirubinemia, maRali BUN, maRali

bilirubinemia, maRali BUN, maRali kreatinini, abnormaluri Sexorceba, hiperglikemia, hiperkalemia, hipokalemia,

13

kreatinini, maRali enzimis done (laqtikuri dehidrogenaza, SGOT da SGPT), hidroqolesterolemia, hiperglikemia, hiperkalemia, hiperlipemia, hiperurikemia, hipervolemia, hipokalemia, hipomagnezimia, hiponatremia, wonis momateba

hipokalcemia, hipokalemia, hipoglikemia, hipomagnezimia, hipofosfatemia, hipoproteinemia




gulis gadanergviT

(n=289)**


3-<10% acidozi (metabolikuri an raspiratoruli) momatebuli alkalainis fosfataza, dehidracia, enzimis maRali done (gamma glutamilis transpeptidaza, laqtikuri dehidrogenaza, SGOT da SGPT), maRali kreatinini, hiperkalcemia, hiperlipemia, hipervolemia, hipokalcemia, hipoglikemia, hipoproteinemia, hiperurikemia, wonis momateba

abnormaluri Sexorceba, momatebuli alkalainis fosfataza, alkalozi, dehidracia, nikrisi, hipokalcemia, hipoqloremia, hipoglikemia, hipoproteinemia, hipofosfatemia, hipovolemia, hipoqsia, respiratoruli acidozi, wyurvilis grZnoba, wonis dakargva

acidozi (metabolikuri an raspiratoruli) momatebuli alkalainis fosfataza, dehidracia, enzimis maRali done (SGOT da SGPT), hiperqolesteremia, hiperlipemia, hiperfosfatemia, hipervolemia, hiponatremia, hipoqsia, hipovolemia, wonis momateba, wonis dakleba

kuW-nawlavis/gastrointestinaluri

≥10% kuWis Sekruloba, diarea, dispepsia, nauzea da Rebineba,

kuWis Sekruloba, diarea, dispepsia,

RviZlis funqciis momatebuli testi (AST da ALT CaTvliT), anoreqsia, qolangiti,

14

oraluri kandidozi

gazebi, nauzea da Rebineba, oraluri kandidozi

qolestatiuri siyviTlis konstipacia, diarea, dispepsia, gazebi, hepatiti, nauzea da Rebineba, oraluri kandidozi

3-<10% RviZlis funqciis momatebuli testi (AST da ALT

CaTvliT), anoreqsia, gazebi, gastroenteriti, sisxldena, kuWnawlavis kandidozi, gingiviti, nawlavebis hiperplazia, hepatiti, nawlavebis gauvaloba, ezofagiti, stomatiti

RviZlis funqciis momatebuli testi (AST da ALT CaTvliT), anoreqsia, disfagia, gastroenteriti, gingiviti, nawlavebis hiperplazia, siyviTle, melena, ezofagiti, stomatiti

disfagia, gastriti, gastrointestinaluri sisxldena, nawlavebis gauvaloba, siyviTle, melena, piris dawyluleba, ezofagiti, Tirkmlebis funqciis darRveva, kuWis wyluli

raspiratoruli

≥10% momatebuli xvela, dispnea, faringiti, pnevmonia, bronqiti

asTma, momatebuli xvela, dispnea, faringiti, plevraluri efuzia, pnevmonia, riniti, sinusiti

ateleqtazi, momatebuli xvela, dispnea, faringiti, plevraluri efuzia, pnevmonia, sinusiti




gulis gadanergviT

(n=289)**


3-<10% asTma, plevraluri efuzia, pulmonaruli edema, riniti, sinusiti

apnoe, ateleqtazi, bronqiti, cxviridan sisxldena, hemoftizi,

asTma, bronqiti, cxviridan sisxldena, hiperventilacia, pnevmoToraqsi, pulmonaruli edema, raspiratoruli

15

slokini, neoplazma, pnevmoToraqsi, pulmonaruli edema, naxvelis momateba, xmis Secvla

moniliazi, riniti

kani da danamatebi

≥10% akne, Cveulebrivi herpesi

akne, Cveulebrivi herpesi, herpes zosteri, gamonayari

qavili, gamonayari, oflianoba

3-<10% alopecia, kanis keTilTvisebiani neoplazma, fungaluri dermatiti, herpes zosteri, WarbTmianoba, qavili, kanis karcinoma, kanis hipertrofia (aktinikuri keratozis CaTvliT), oflianoba, kanis wyluli, gamonayari

kanis keTilTvisebiani neoplazma, fungaluri dermatiti, sisxldena, qavili, kanis karcinoma, kanis hipertrofia, kanis wyluli, oflianoba

akne, fungaluri dermatiti, sisxldena, Cveulebrivi herpesi, herpes zosteri, WarbTmianoba, kanis keTilTvisebiani neoplazma, kanis wyluli, vesikulobulozuri gamonayari

nervuli ≥10% Tavbrusxveva, uZiloba, kankali

aRgznebuloba, SfoTva, konfuzia, depresia, Tavbrusxveva, hipertonia, uZiloba, paresTezia, Zilianoba, kankali

SfoTva, konfuzia, depresia, Tavbrusxveva, uZiloba, paresTezia, kankali

3-<10% SfoTva, depresia, hipertonia, paresTezia, Zilianoba

konvulsiebi, emociuri aramdgradoba, halucinaciebi, neuropaTia, abnormaluri fiqri, Tavbrusxveva

aRgznebuloba, konvulsiebi, bodva, piris simSrale, hipertonia, hipesTezia, neiropaTia, fsiqozi, Zilianoba, abnormalrui fiqri

Zval-kunTovani

≥10% - fexis krunCxva, mialgia, miasTenia

-

3-<10% arTralgia, fexis krunCxva, mialgia, miasTenia

arTralgia arTralgia, fexis krunCxva, mialgia, miasTenia, osTeoporozi

mgrZnobelobis organoebi

≥10% - gaoreba -

3-<10% gaoreba, kataraqta,

abnormaluri xedva,

abnormaluri xedva, gaoreba, koniuqtiviti,

16

koniuqtiviti koniuqtiviti, siyrue, Tvalis tkivili, Tvalis sisxldena, tinitusi

siyrue

endokrinuli

≥10% - - -

sxeulis sistema gverdiTi

movlenebi pacientebSi Tirkmlis



gulis gadanergviT

(n=289)**


endokrinuli

3-<10% diabet melitusi, paraTiroiduli darRveva (PTH-is maRali done)

diabet melitusi, kiuSingis sindromi, hipoTiroidizmi

diabet melitusi

* (mTliani raodenoba n=1,485) ** (mTliani raodenoba n =578) *** (mTliani raodneoba n =564) Tirkmlis gadanergvisas mocilebisas sami kontrolirebadi cdisas, pacientebs, romlebic Rebulobdnen selseptis 2 grams dReSi, gamoumJRavndaT mTlianobaSi ukeTesi mdgomareoba, vidre pacintebs, romlebic Rebulobdnen selseptis 3 grams dReSi. 2.6.2 postmarketinguli gamocdileba gastrointestinaluri: koliti (zogjer gamowveuli citomegalovirusiT), pankreatiti, nawlavebis vilualuri atrofia calkeul SemTxvevebSi. imunosupresiis darRveva: sicocxlisaTvis saSiSi infeqciebi, rogoricaa meningiti da endokarditis infeqcia, gamomJRavnda zogierT SemTxvevaSi; aris zogierTi tipis infeqciis maRali sixSire, rogoricaa tuberkulozi da aTipiuri mikobaqteriuli infeqcia. selseptiT namkurnaleb pacientebSi aRwerilia progresuli multifokaluri leikoencefalopaTiis (pml) SemTxvevebi, romelic zogjer fataluri gamosavliT SeiZleba dasruldes. Tirkmel-gadanergili pacientebis selseptiT mkurnalobis dros aRwerilia bk-virusTan asocirebuli nefropaTiis SemTxevevebi. es aris seriozuli infeqciuri garTuleba, romelmac SeiZleba gamoiwvios gadanergili organos dazianeba. selseptiT sxva imunosupresorebTan kombinaciaSi mkurnalobis dros SesaZlebelia ganviTardes wiTeli ujredebis WeSmariti aplazia

17

Tandayolili darRvevebi/simaxinjeebi: Tandayolili simaxinjeebi yuris simaxinjis CaTvliT gamomJRavnda pacientebis STamomavlebSi, romlebsac miRebuli hqondaT MMF-is kombinacia sxva imunosupresantebTan erTad orsulobisas. sxva gverdiTi movlenebi selseptis post-marketinguli gamocdilebisas msgavsia imisa, rogoric gamomJRavnda Tirkmlis, gulis da RviZlis gadanergvisas gamokvlevis dros. 2.7. dozis gadaWarbeba mikofenolat mofetilis dozis gadaWarbebaze Sedegebi miRebuli iqna klinikuri gamokvlevisas da post-marketinguli gamocdilebidan. am SemTxvevebSi ar aris gamomJRavnebuli gverdiTi movlenebi. dozis gadaWarbebis im SemTxvevebSi, rodesac miRebulia gverdiTi movlenebi, Sedegebi moqceulia wamlis usafrTxoebis cnobil aRweraSi. mosalodnelia rom mikofenolat mofetilis dozis gadaWarbebam iqonios Sedegi imunuri sistemis zedmet daxSobaSi da gazardos infeqciebis mimarT mgrZnobeloba da AZvlis tvinis supresia (ix. 2.4 gafrTxileba da sifrTxilis zomebi). im SemTxvevaSi, Tu ganviTarda neitropenia, selseptis dozireba unda Sewydes an doza Semcirdes (ix. 2.4 gafrTxileba da sifrTxilis zomebi). MPA ar Sordeba hemodializiT. amgvarad, MPAG-is plazmis koncentraciisas (>100µg/ml) MPAG-is mcire odenoba Sordeba. naRvelis mJavis sekvestrants, rogoricaa qolesteramini, SeuZlia -MPA-s moSoreba wamlis gamoyofis gazrdiT (ix.3.2 farmakokinetikuri maxasiaTeblebi). 3. farmakologiuri maxasiaTeblebi da Tvisebebi

3.1. farmakodinamikuri maxasiaTeblebi 3.1.1 moqmedebis meqanizmi mikofenolat mofetili (MMF) aris mikofenolis mJavis (MPA) 2- morfolinoeTilis eTeri. MFA aris inozinmonofosfat dehidrogenazas Zlieri, seleqtiuri, arakonkurentuli Seqcevadi inhibitori, romelic Trgunavs guanozin nukleotidebis dehidrogenazas (IMPDH) da amrigad aferxebs guanozin nukleotidis sinTezs Tavidan. meqanizmi, romliTac MPA aferxebs IMPDH–is enzimur aqtivobas, rogorc Cans dakavSirebulia MPA–s TvisebasTan struqturulad daemsgavsos rogorc nikotinamid adeninis dinukleotidis kofaqtors da aseve wylis katalitikur molekulas. es aridebs IMP–is Jangvas qsantoza-5’ –monofostatTan, romelic aris gardamavali nabiji guanozin nukleotidis biosinTezis ganmeorebis dros. MPA–s gaaCnia ufro Zlieri citostatikuri gavlena limfocitebze, vidre sxva ujredebs, vinaidan T- da B- limfocitebis proliferacia kritikulad damokidebulia purinebis ganmeorebiT (axal) sinTezSi, radgan ujredebis sxva saxeobas SeuZliaT gamoiyenon gadarCenis gzebi. 3.1.2 klinikuri/efeqturobis Semswavleli kvlevebi klinikuri kvlevebSi selsepti miiReboda Semdegi agentebis kombinaciaSi Tirkmlis, gulis da RviZlis mocilebis SemTxvevebSi: antitimocituri

18

globulini, OKT3, ciklosforini da kortikosteroidebi. selsepti aseve miiReboda ciklosporinTan da kortikosteroidebTan kombinaciaSi Tirkmlis refraqtoruli mocilebis SemTxvevebis mkurnalobisas. selseptiT mkurnalobis dawyebamde, pacientebs SesaZlebelia miRebuli hqonodaT antilimfocitis globulini, antitimocitis globulini da OKT3.

selsepti Semdgom gamoiyeneboda klinikur cdebSi daklicumabTan da takrolimusTan erTad. organoebis mocilebis Tavidan acileba selseptis usafrTxoeba da efeqturoba kortikosteroidebTan da ciklosforinTan kombinirebiT organoebis mocilebis Tavidan asacileblad Sefasebul iqna Tirkmlis gadanergvisas sam SemTxveviT, ormagi-brma, multicentruli cdebiT; gulis pacientebSi erT SemTxveviT, ormagi-brma, multicentrul cdaSi; RviZlis pacientebSi erT SemTxveviT, ormagi-brma, multicentrul cdebSi. Tirkmlis gadanergva sami cda Sedarebuli ori dozis donesTan oraluri selseptisTvis (1 grami orjer dReSi da 1.5 grami orjer dReSi) azaTioprinTan (2 gamokvleva) an placebo (1 gamokvleva) rodesac miiReboda ciklosforinTan da kostikosteroidebTan kombinaciaSi mwvave mocilebis SemTxvevebis Tavis asarideblad. pirveladi efeqturobis saboloo wertili iyo pacientebis proporcia TiToeul samkurnalo jgufSi ori gamocdili mkurnalobis warumatebeli gadanergvis Semdeg 6 Tvis vadaSi (ganisazRvreba rogorc biofsiiT dadasturebuli mwvave mocileba sikvdilis, qsovilis dakargvis an dakvirvebisas nebismieri mizeziT adreuli dasrulebis SemTxvevebSi, biofsiiT winaswar dadasturebuli mocilebis gareSe). selsepti Seswavlili iyo Semdegi sami Terapevtuli reJimis dros: (1) antiTimocitis globulinis induqcia/MMF an azaTioprini/ciklosforini/kostikosteroidebi, (2) MMF an azaTiorpini/ciklosforini/kortikosteroidebi, da (3) MMF an placebo/cikloforini/kortikosteroidebi. selsepti kortikosteroidebTan da ciklosforinTan kombinaciaSi amcirebda (statistikurad mniSvnelovan <0.05 doneze) mkurnalobis warumateblobis SemTxvevas gadanergvis Semdeg 6 Tvis periodSi. qvemoT cxrilSi dajamebulia am Seswavlis Sedegebi. pacientebi, romlebmac winaswar Sewyvites mkurnaloba, daiRupnen an ganicdidnen qsovilis dakargvas; qsovilis dakargvis kumulatiuri SemTxvevebi da pacientis daRupva jamdeba calke. pacientebs, romlebmac droze adre Sewyvites mkurnaloba, ar CautardaT dakvirveba Sewyvetis Semdeg mwvave mocilebaze. pacientebis metma nawilma, romlebic Rebulobdnen selsepts, Sewyvites (biofsiiT winaswar damtkicebuli mocilebisas, daRupvisas an qsovilis dakargvisas) kontrolirebad jgufebSi, jgufSi selseptis yvelaze maRali doziT 3 grami/dReSi. amgvarad mwvave mocilebis maCvenebeli SeiZleba iyos Semcirebulad Sefasebuli, gansakuTrebiT selseptis jgufSi misi miRebiT 3 grami/dReSi odenobiT. Tirkmlis gadanergvis Seswavla

19

mkurnalobis warumateblobis SemTxvevebi (biofsiiT dadasturebuli mocileba an adreuli Sewyveta nebismieri mizeziT) aSS kvleva * (n=499 pacienti)

selsepti 2 grami /dReSi (n=167 pacienti)


azaTioprini 1 dan 2 mg/kg/dReSi (n=166 pacienti)

yvela mkurnalobis warumatebloba

31.1% 31.3% 47.6%

adreuli Sewyveta winaswari mwvave mocilebis gareSe**

9.6% 12.7% 6.0%

biofsiiT dadasturebuli mocilebis SemTxvevebi mkurnalobisas

19.8% 17.5% 38.0%

*antitimocituri globulinis induqcia/MMF an azaTioprini/ciklosporini/kortikosteroidebi

evropa/kanada/avstraliis kvleva * (n=503 pacienti)



azaTioprini 100dan 150 mg/dReSi (n=166 pacienti)


38.2% 34.8% 50.0%


13.9% 15.2% 10.2%

biofsiiT dadasturebuli mocilebis SemTxvevebi mkurnalobisas

19.7% 15.9% 35.5%

*MMF an azaTioprini/ciklosporini/kortikosteroidebi

evropis kvleva * (n=491 pacienti)



placebo (n=166 pacienti)


30.3% 38.8% 56.0%


11.5% 22.5% 7.2%

biofsiiT 17.0% 13.8% 46.4%

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dadasturebuli mocilebis SemTxvevebi mkurnalobisas *MMF an placebo/ciklosporini/kortikosteroidebi ** ar moicavs daRupvas da qsovilis dakargvas rogorc adreuli Sewyvetis mizezs.

12-Tviani qsovilis dakargvis kumulatiuri SemTxveva da pacientis daRupva mocemulia qvemoT. selseptis aranairi damokidebuleba qsovilis dakargvasTan an pacientis daRupvasTan dakavSirebiT ar aris dadasturebuli. raodenobrivad, pacientebi, romlebic Rebulobdnen selsepts 2 grams/dReSi da 3 grams/dReSi gamouvlindaT saukeTeso Sedegi, vidre kontrolis dros samive cdaSi; pacientebs, romlebic Rebulobdnen selseptis 2 grams/dReSi gamouvlindaT ukeTesi Sedegi, vidre doziT selsepti 3 grami/dReSi or SemTxvevaSi sami Seswavlisas. pacientebs samive mkurnalobis jgufSi, romlebsac SeuwydaT mkurnaloba adre, gamoumJRavndaT susti Sedegi qsovilis dakargvasTan da pacientis daRupvasTan dakavSirebiT pirveli weliwadis ganmavlobaSi. Tirkmlis gadanergvis gamokvleva qsovilis dakargvis kumulatiuri SemTxveva da pacientis daRupva 12 Tvis periodis ganmavlobaSi

gamokvleva selsepti 2 grami/dReSi

selsepti 3 grami/dReSi

kontroli (azaTioprini an

placebo) aSS 8.5% 11.5% 12.2% evropa/kanada/avstralia 11.7% 11.0% 13.6% evropa 8.5% 10.0% 11.5% gulis gadanergva pacientebSi gulis gadanergviT Catarda ormagi-brma, SemTxveviTi, SedarebiTi, multicentruli gamokvleva gulis pirveladi gadanergvis mqone pacientebSi. monawile pacientebis saerTo raodenoba iyo 650; 72 arasdros hqonda miRebuli wamali da 578 miRebuli hqonda Sesaswavli wamali. pacientebi Rebulobdnen selsepts 1.5 gramiT orjer dReSi (n=289) an azaTioprins 1.5dan 3mg/kg/dReSi (n=289) ciklosforinTan da kortikosteroidebTan kombinaciaSi, rogorc mxardamWeri imunosupresoris Terapias. ori saboloo efeqturobis wertili: (1) im pacientebis proporcia, romlebsac gadanergvis Semdeg gaaCndaT aranakleb erTi endomiokardiuli biofsiiT dadasturebuli mocileba hemodinamikuri SeRavaTiT, an gaaCndaT gadanergva da daiRupnen, pirveli 6 Tvis periodis ganmavlobaSi, da (2) pacientebis proporcia romlebic daiRupnen an gaaCndaT gadanergva pirveli 12 Tvis periodis ganmavlobaSi gadanergvis Semdeg. pacientebs, romlebmac adreulad Sewyvites mkurnaloba, gamoumJRavndaT alograftuli mocileba 6 Tvemde periodis ganmavlobaSi da daRupvis SemTxvevebi 1 wlamde periodis ganmavlobaSi. 1. mocileba: ar aris dadgenili sxvaoba selsepts da azaTioprinTan (AZA) biofsiiT dadasturebuli mocilebisas kavSiri hemodinamikuri SeRavaTiT, rogorc naCvenebia qvemoT.

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ukugdeba 6 Tvis periodis ganmavlobaSi yvela pacienti mkurnali pacientebi

AZA

N=323 selsepti

N=323 AZA

N=289 selsepti

N=289 biofsiiT dadasturebuli mocileba hemodimikuri SeRavaTiT*

121 (38%) 120 (37%) 100 (35%) 92 (32%)

* hemodinamikuri SeRavaTis SemTxvevebs aqvT adgili Tuki daculia Semdegi kriteriumebidan romelime: pulmonaruli kapilaruli solis wneva ≥20 mm an 25%-iT momatebulia; gulis indeqsi <2.0 l/wuTSi/m2 an 25%-iT Semcirebulia; mocilebis fraqcia ≤30%-ze; pulmonaruli arteriis JangbadiT gajereba ≤60%-ze an 25%-iT Semcirebulia; S3

gamwvavebis arseboba; fraqciuli Semcireba ≤20%-ze an 25%-iT Semcirebulia; inotropuli mxardaWera aucilebelia klinikuri mdgomareobis marTvisas.

2. gadarCena: monawile pacientebSi, sadac ar iyo arsebiTi sxvaoba MMF-is SemTxveviT pacientebs Soris da AZA s SemTxveviT pacientebs Soris daRupvisas da retransplantaciisas. pacientebSi, romlebic Rebulobdnen gamosakvlel wamals, umciresi limitiT 97.5% Tanxvedris intervaliT sxvaoba daRupvasa da retransplantaciisas iyo 0.9 pirveli wlis periodis ganmavlobaSi, MMF-is ufro maRali maCvenebliT vidre AZA pacientebSi, rogorc es naCvenebia qvemoT.

daRupva gadanergvisas pirveli wlis ganmavlobaSi

yvela pacienti mkurnali pacientebi AZA

N=323

selsepti n=327

AZA

N=289 selsepti

n=289 daRupva an retransplantacia

49 (15.2%) 42 (12.8%) 33 (11.4%) 18 (6.2%)

mkurnalobis Sefasebuli sxvaoba

2.6% 5.3%

umciresi limiti 97.5% calmxrivi Tanxvedris periodi

-2.5% +0.9%

RviZlis gadanergva: ormagi-brma, SemTxveviTi, SedarebiTi, paralelur-jgufuri, multicentruli gamokvleva RviZlis pirveladi gadanergvis mimReb pacientebSi, romelic ganxorcielda 16 centrSi aSS-Si, 2- kanadaSi, 4- evropaSi da 1 – avstraliaSi. monawile pacientebis saerTo ricxvi iyo 565 da 564–ma miiRo samkurnalo wamali. pacientebi Rebulobdnen an selsepts 1 grams orjer dReSi intravenurad 14 dRemde periodSi, Semdgomi 1.5 grami selseptis miRebiT orjer dReSi oralurad; an azaTiorpinis 1-2

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mg/kg/dReSi intravenurad azaTiorpinis Semdgomi 1-2 mg/kg/dReSi miRebiT oralurad, ciklosforinTan da kortikosteroidebTan kombinaciaSi, rogorc imunosupresiis Terapiis mxardaWera. ori saboloo wertili: (1) im pacientebis proporcia, romlebsac gaaCndaT gadanergvis Semdeg 6 Tvis ganmavlobaSi biofsiiT dadasturebuli erTi an ori mocilebis mkurnalobis SemTxveva an daRupva/retransplantacia da (2) im pacientebis proporcia, romlebsac gaaCndaT qsovilis dakargva (daRupva/retransplantacia) gadanergvis Semdeg 12 Tvis ganmavlobaSi. pacientebi, romlebmac droze adre Sewyvites mkurnaloba da gamoumJRavndaT alograftuli mocileba da qsovilis dakargva (daRupva/retransplantacia) erTi wlis periodis ganmavlobaSi. Sedegebi: pirveladi (mizezi-Sedegi) analizis Sedegad selsepti kombinirebisas kortikosteroidebTan da ciklosforinTan iyo ufro ukeTesi, vidre azaTiorpini mwvave mocilebis Tavidan asacileblad (p=0.025); xolo eqvivalenturi azaTiorpinTan – gadarCenisaTvis.

mocileba 6 Tvis periodis ganmavlobaSi daRupva an retransplantacia 1 wlamde periodis ganmavlobaSi AZA n=287 selsepti n=278 biofsiiT dadasturebuli namkurnalevi mocileba 6 Tvis periodis ganmavlobaSi

137 (47.7%) 107 (38.5%)

daRupva an retransplantacia 1 wlis ganmavlobaSi

42 (14.6%) 41 (14.7%)

organos refraqtoruli mocilebis mkurnaloba SemTxveviTi, Ria Sedarebis gamokvleva MMF-Si 3 grami/dReSi intravenuri kortikosteroidebis sawinaaRmdegod Catarebul iqna 150 Tirkmlis gadanergvis mqone pacientSi refraqtoruli, mwvave, ujreduli alografuli mocilebiT. pirveladi saboloo wertili iyo im pacientebis proporcia, romlebic jer kidev iyvnen cocxlebi funqcionirebadi qsoviliT 6 Tvis periodis ganmavlobaSi gamokvlevaSi monawileobis Semdeg. Sedegebi: qsovilis dakargvis SemTxvevebi kontrolirebad jgufebSi iyo moulodnelad mcire da pirveladma analizma, romelic dafuZnebulia seqvenciur savaraudo Tanafardobis cdaze gamoamJRavna gaumjobesebuli qsovilis gadarCenis tendencia MMF jgufSi (p=0.081). meoradma analizma, koqran-mantel-henzelis (Cochran-Mantel-Haenzel) testis gamoyenebiT (romelic ar dakoreqtirda seqventoruli monitoringisTvis) aCvena qsovilis dakargvis an daRupvis Semcireba 45%-iT 6 Tvis periodis ganmavlobaSi gamokvlevis Semdeg MMF–is SemTxvevaSi (p=0.062). qsovilis dakargva an daRupva 6 Tvis periodis ganmavlobaSi intravenuri

steroidebi N=73

selsepti N=77

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qsovilis dakargva an daRupva 6 Tvis periodis ganmavlobaSi

19 (26.0%) 11 (14.3%)

3.2. farmakokinetikuri maxasiaTeblebi MMF-is farmakokinetika Seswavlil iqna Tirkmlis, gulis da RviZlis gadanergvis mqone pacientebSi.

ZiriTadad, MPA-s farmakokinetikuri profili msgavsia Tirkmlis da gulis gadanergvis mqone pacientebSi. gadanergvis adreul periodSi, RviZlis gadanergvis mqone pacientebi, romlebic Rebuloben MMF-is 1.5 oralur dozas an 1 g.i.v MMF-is dozas msgavsad MPA donisa, Tirkmlis gadanergvis mqone pacientebTan SedarebiT, romlebic Rebuloben 1 gram MMF-s oralurad an intravenurad. 3.2.1. Sewova oraluri an intravenuri miRebisas, mikofenolat mofetili ganicdis swraf da farTo Sewovas da sruldeba presistemuri metabolizmi aqtiuri metabolitebis mier, MPA. oraluri mikofenolat mofetilis mwiri biogamosadegoba, romelic dafuZnebulia MPA AUC-ze, aris 94% dakavSirebuli intravenur mikofenolat mofetilTan. mikofenolat mofetili SeiZleba gaizomos sistematiurad intravenuri infuziisas; amrigad, oraluri miRebis Semdeg is aris raodenobrivi analizis limits qvemoT (0.4 µl/ml). uSualod gadanergvis Semdeg (<40 dRe) Tirkmlis, gulis da RviZlis gadanergvis mqone pacientebs gaaCndaT MPA AUC daaxloebiT 30%-iT mcire da Cmax daaxloebiT 40%-iT Semcirebuli gviandel gadanergvis periodTan SedarebiT (3-6 Tve gadanergvis Semdeg). MPA AUC–is Sefaseba Sesrulebulia intravenurad selseptis 1 gramis orjer dReSi miRebis mixedviT, rekomendebuli infuziis doniT, Tirkmlis gadanergvis mqone pacientebSi uSualod gadanergvis Semdgom fazaSi, romlebic Sesadarebelia igive maCvenebelTan oraluri dozirebis Semdeg. RviZlis gadanergvis mqone pacientebSi, intravenuri selseptis 1 gramis orjer dReSi miReba Semdgomi 1.5 grami orjer dReSi selseptis oraluri miRebiT, MPA AUC Sefasebisas msgavsia imisa, romelic mopovebulia pacientebSi Tirkmlis gadanergviT, romlebic Rebulobdnen 1 gram selsepts dReSi orjer. sakvebs ar gaaCnia gavlena mikofenolat mofetilis Sewovis doneze (MPA

AUC) romelic miiReba doziT 1.5 grami dReSi orjer Tirkmlis gadanergvis mqone pacientebSi. amrigad, Cmax Semcirda 40%-iT sakvebis miRebis SemTxvevaSi. 3.2.2 ganawileba plazmis MPA koncentraciis meoradi zrda Cveulebriv Seswavlilia daaxloebiT 6-12 saaTis ganmavlobaSi dozirebis Semdeg, enterohepaturi recirkulaciis Sesabamisad. Semcireba daaxloebiT 40%-iT MPA AUC–Si dakavSirebulia qolestiraminis erTdoulad miRebiT (4 grami samjer dReSi), enterohepatiuri recirkulaciis Sewyvetis Sesabamisad.

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klinikurad Sesabamis koncentraciebSi, MPA udris 97%-s romelic uerTdeba plazma albumins. 3.2.3 metabolizmi MPA erTiandeba pirvel rigSi glukuronil transferazas MPAs fenolikuri glukuronidis sawarmoeblad (MPAG), romelic ar aris farmakologiurad aqtiuri. organizmSi, MPAG iqceva Tavisufal MPA- enTerohepatiuri recirkulaciis meSveobiT. 3.2.4 gamoyofa radiolabeluri mikofenolat mofetilis oraluri miRebis Sedegi iyo sruli gankurnva gamowerili dozis dros, dozis 93% gamoyofiT SardSi da 6%-is gamoyofiT fekalur masaSi. dozis umetesi nawili (daaxloebiT 87%) gamoiyofa SardSi, rogorc MPAG. wamlis umniSvnelo nawili (dozis 1%–ze naklebi) gamoiyofa MPA–d SardSi. koncentraciebSi klinikur SemTxvevebSi, MPA da MPAG ar Sordeba hemodializis dros. amrigad, MPAG-s maRali koncentraciisas (>100 µl/ml) Sordeba MPAG–s mcire odenoba. wamlis enTerohepatiuri cirkulirebis Seferxebisas, naRvelis mJavis seqvestrantebi, rogoricaa qolestiramini, amcireben MPA AUC–s (ix. 2.7 dozis gadaWarbeba). 3.2.5 bioeqvivalentoba Sefasebulia selseptis oraluri dozebis bioeqvivalentobis formebi. ori 500 mg-iani tableti aris oTxi 250mg-iani kafsulis bioeqvivalenturi. 3.2.6. farmakokinetika gansakuTrebul SemTxvevebSi pacientebi Tirkmlis mZime dazianebiT erTjeradi dozis Seswavlisas (6 subieqti jgufSi), gamokvleuli iyo mikofenolis mJavis SratSis AUC-is saSualo maCvenebeli. subieqtebSi Tirkmlis mZime qronikuli dazianebiT (glomerularuli filtraciis koeficienti (<25ml/wT/1.73 m2) iyo 28-75%-iT ufro maRali vidre is, romelic gamomJRavnda normalur janmrTel subieqtebSi an subieqtebSi Tirkmlis dazianebis naklebi xarisxiT. amgvarad, AUC iyo 3- 6-jer ufro maRali subieqtebSi Tirkmlis mZime dazianebiT, vidre subieqtebSi Tirkmlis saSualo dazianebiT da normalur janmrTel subieqtebSi, romelic Seesabameba MPAG-s cnobil Tirkmlis mocilebaSi. mikofenolatis mofetilis mravaljeradi dozireba pacientebSi Tirkmlis mwvave qronikuli daqveiTebisas ar aris Seswavlili. pacientebi Tirkmlis gadanergvis Semdeg transplantantis gadavadebuli funqcionirebiT pacientebSi Tirkmlis transplantantis gadavadebuli funqcionirebiT gadanergvis Semdeg, mwiri MPA AUC0-12 SedarebiTia imasTan, romelic gamoaSkaravda gadanergvis mqone pacientebSi, romlebsac ar gaaCndaT Tirkmlis gadavadebuli graftuli funqcia. SesaZlebelia adgili hqondes gardamaval zrdas Tavisufal fraqciaSi da MPA plazmis koncentracias pacientebSi Tirkmlis gadavadebuli graftuli funqciiT. selseptis dozis dazusteba ar gaxda aucilebeli (ix. 2.2.1 specialuri dozirebis

25

instruqcia). mwiri MPAG AUC0-12 plazma iyo 2- 3-jer ufro maRali, vidre pacientebSi gadanergvis Semdgom, romlebsac ar gaaCndaT Tirkmlis gadavadebuli graftuli funqcia. pacientebSi pirveladi ara funqcionirebadi qsoviliT Tirkmlis gadanergvis Semdeg, MPAG-is plazmis koncentracia dagrovda; MPA-s dagroveba, amgvaris arsebobis SemTxvevaSi, iyo metad mcire. pacientebi RviZlis daqveiTebiT MPAs da MPAGs saerTo farmakokinetikaze SedarebiT gavlena ar iqonia RviZlis parenqimalurma daavadebam, moxaliseebSi alkoholuri ciroziT, romlebsac daeniSnaT MMF–is oraluri an intravenuri dozireba. RviZlis daavadebis efeqti am procesebze savaraudod damokidebulia maT garkveul daavadebaze. RviZlis daavadebas ZiriTadad naRvelis dazianebiT, rogoricaa naRvelis pirveladi cirozi, SeiZleba gaaCndes gansxvavebuli efeqti. asakovani pacientebi/moxucebi (≥65 weli) farmakokinetika moxucebSi ar aris formalurad Sefasebuli. 3.3 wina klinikuri usafrTxoeba sisxlmwarmoebeli da limfoiduri sistemebi aris pirveladi organoebi, romlebzedac gavlenas axdens toqsikologiuri Seswavla; is iwarmoeba mikofenolat mofetilis saSualebiT virTxebSi, TagvebSi, ZaRlebSi da maimunebSi. am efeqtebs adgili aqvT sistemuri gamovlinebis doneebSi, romlebic metnaklebad klinikuri gamovlinebis eqvivalenturia rekomendebuli doziT 2 grami/dReSi pacientebSi Tirkmlis gadanergviT. kuWnawlavis efeqti gamomJRavnda ZaRlebSi sistemuri gamomJRavnebis doneze, romelic aris klinikuri gamomJRavnebis metnaklebad eqvivalenturi rekomendebuli dozirebisas. dehidraciasTan dakavSirebuli gastrointestinaluri da Tirkmlis efeqtebi aseve gamomJRavnda maimunebSi umaRlesi dozis miRebisas (sistemuri gamomJRavnebis done eqvivalenturi an ufro meti, vidre klinikuri gamovlineba). mikofenolat mofetilis araklinikuri toqsikurobis profili mJRavndeba, rogorc Sesaferisi arasasurvel SedegebSi adamianis klinikur cdebSi, romelic amJamad warmoadgens usafrTxoebis ufro Sesabamis informacias pacientebis mosaxleobasTan dakavSirebiT (ix. 2.6. arasasurveli efeqtebi). 3.3.1 fertilobis dazianeba mikofenolat mofetils ar gaaCnia gavlena mamri virTxebis nayofierebaze oraluri dozebis miRebisas 20 mg/kg/dReSi. am dozis miRebisas sistemuri gamovlineba warmoadgens 2-dan 3 klinikur gamomJRavnebas rekomendebuli klinikuri dozis miRebisas 2 grami/dReSi Tirkmlis gadanergvis mqone pacientebSi da 1.3.-2 klinikuri gamovlineba rekomendebuli klinikuri dozis miRebisas 3 grami/dReSi gulis gadanergvis mqone pacientebSi. qalebis nayofierebaze da reproduqtiulobaze gamokvlevisas virTxebSi, oralurma dozirebam 4.5. mg/kg/dReSi gamoiwvia simaxinjeebi (anoftalmiis, agnaciis da hidrocefaliis CaTvliT) pirveli Taobis STamomavlobaSi

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dedis toqsikurobis ararsebobisas. am dozis sistemuri gamovlineba iyo daaxloebiT 0.5 klinikuri gamovlinebisas rekomendebuli klinikuri dozis miRebisas 2 grami/dReSi pacientebSi Tirkmlis gadanergviT da daaxloebiT 0.3 klinikuri gamovlineba rekomendebuli klinikuri dozis miRebisas 3 grami/dReSi gulis gadanergvis mqone pacientebSi. ar aris SemCneuli gavlena nayofierebis an reproduqtiulobis parametrebze mdedrebSi da Semdgom TaobebSi. 3.3.2 teratogenuroba teratologiuri kvlevisas virTxebSi da bocverebSi, iyo nayofis rezorpciis da simaxinjeebis SemTxvevebi; virTxebSi 6 mg/kg/dReSi (anoftalmiis, agnaciis da hidrocefaliis CaTvliT) da bocverebSi 90 mg/kg/dReSi (kardiovaskularuli da Tirkmlis anomaliebis, rogoricaa eqtopia kordis da eqtopiuri Tirkmlebi, da diafragmuli da Sedgenili Tiaqaris CaTvliT) dedis toqsikurobis ararsebobis SemTxvevaSi. am doneebze sistemuri gamovlineba daaxloebiT eqvivalenturia meti an naklebi 0.5 klinikuri gamovlinebisa rekomendebuli klinikuri dozis dros 2 grami/dReSi Tirkmlis gadanergvis mqone pacientebSi da daaxloebiT 0.3 klinikuri gamovlinebisa rekomendebuli klinikuri doziT 3grami/dReSi gulis gadanergvis mqone pacientebSi. ix. seqcia 2.5.1 orsuloba 3.3.3 damatebiTi eqsperimentul modelebSi, mikofenolat mofetili ar iyo simsivneebis warmomqmneli. umaRlesma dozam, romelic gamocdili iyo cxovelebze karciogeniciurobis kvlevisas, iqonia Sedegi daaxloebiT 2-3 jer sistemuri gamomJRavnebisas (AUC an Cmax) pacientebSi Tirkmlis gadanergviT rekomendebuli klinikuri doziT 2 grami/dReSi da 1.3-2 jer sistemuri gamomJRavnebisas (AUC an Cmax) gulis gadanergvis mqone pacientebSi rekomendebuli klinikuri doziT 3 grami/dReSi. genotoqsikurobis orma kvlevam (Tagvis limfoma/timidinis kinazis kvleva da Tagvis mikronukleuri gadaxris kvleva) gamoavlina mikofenolat mofetilis SesaZlebloba, gamoiwvios qromosomuli arastabiluroba mwvave citotoqsikuri dozis doneze. sxva genotoqsikurobis cdebma (baqteriuli mutaciis cda, safuaris mitotikuri genis konverciis cda an Cinuri zazunas sakvercxis ujredis qromosomuli aberaciis cda) ar gamoavlina mutagenuri aqtivoba. 4. farmacevtuli maxasiaTeblebi

4.1 Senaxva selseptis kafsulebi: ar SeinaxoT 250C-ze met temperaturaze, SeinaxeT Tavis yuTSi. selseptis tabletebi: ar SeinaxoT 250C-ze met temperaturaze, SeinaxeT Tavis yuTSi. selsepti intravenuri: fxvnili sainfuzio xsnaris mosamzadeblad: ar SeinaxoT 300C-ze met temperaturaze. gamzadebuli xsnari d xsnari infuziisaTvis: SeinaxeT 15-300C temperaturaze.

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4.2. specialuri instruqcia gamoyenebisa da gankargvisaTvis es wamali ar unda gamoiyenebodes misi vadis gasvlis Semdeg romelic naCvenebia yuTze (EXP). selseptis oraluri miReba vinaidan mikofenolat mofetils gaaCnia teratogenuri efeqti virTxebSi da bocvrebeSi (ix. 2.5.1 orsuloba), selseptis tabletebi ar unda iyos dafSvnili da selseptis kafsulebi ar unda gaixsnas an daifSvnas. Tavi aarideT selseptis kafsulebSi arsebuli fxvnilis SesunTqvas an mis pirdapir kontaqts kanTan an lorwovan garsTan. amgvari kontaqtis SemTxvevaSi, daibaneT kargad sapniT da wyliT; gamoirecxeT Tvali Cveulebrivi wyliT. selseptis intravenuri miReba vinaidan mikofenolat mofetilma gamoamJRavna teratogenuli efeqti virTxebSi da bocverebSi, yuradRebiT udna momzaddes selseptis intravenuri xsnari. Tavi aarideT intravenuri selseptis xsnaris pirdapir kontaqts kanTan an lorwovan garsTan. amgvari kontaqtis SemTxvevaSi, daibaneT kargad sapniT da wyliT; gamoirecxeT Tvali Cveulebrivi wyliT. sainfuzio xsnaris momzadeba (6 mg/ml) intravenuri selsepti ar Seicavs antibaqteriul damcavs; amgvarad, produqtis gaxsna da gazaveba unda ganxorcieldes aseptikur pirobebSi. intravenuri selsepti unda momzaddes or safexurad: pirveli nabiji aris gaxsna 5%-iani deqstrozis intravenuri xsnariT da meore nabiji aris gazaveba 5%-iani deqstrozis intravenuri xsnariT. momzadebis detaluri aRwera mocemulia qvemoT: nabiji 1: a) selseptis ori ampula gamoiyeneba TiToeuli 1 grami dozis mosamzadeblad, sami ampula saWiroa TiToeuli 1.5. grami dozisaTvis. gaazaveT TiToeuli ampulis SigTavsi 14 ml 5%-iani deqstrozis intravenuri infuziiT. b) frTxilad SeanjRrieT ampula wamlis gasaxsnelad odnav moyviTalo xsnaris misaRebad; g) SeamowmeT miRebuli xsnari nawilakebis daSlaze da erTferovnebamde Semdgomi Serevis dawyebamde. ar gamoiyenoT ampula (ampulebi) Tuki masSi SeimCneva nawilakebi an feris Secvla. nabiji 2: a) moamzadeT 1 gramiani doza, Semdeg gaxseniT ori Sedgenili ampula (daaxloebiT 2X15 ml) 140 ml 5%-ian intravenuri deqstrozis xsnarSi. 1.5. grami dozis mosamzadeblad, Semdgom gaxseniT sami Sedgenili ampula (daaxloebiT 3X15 ml) 210 ml 5%-ian intravenuri deqstrozis xsnarSi. orive xsnaris saboloo koncentracia aris daaxloebiT 6 grami mikofenolat mofetili erT ml-ze. b) SeamowmeT infuziis xsnari nawilakebis an feris Secvlis arsebobaze. ar gamoiyenoT ampula (ampulebi) Tuki SeimCneva nawilakebi an feris Secvla.

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gafrTxileba: intravenuri selseptis ineqcia ar unda Catardes swrafad an bolusurad (ix. 2.4 gafrTxileba da sifrTxilis zomebi). im SemTxvevaSi, Tuki infuziis xsnari ar mzaddeba uSualod mis miRebamde, xsnaris infuziis miRebis dawyeba misi Sedgenis Semdeg unda daiwyos wamlis produqtis daSlisa da Sedgenidan 4 saaTis ganmavlobaSi. SeinaxeT xsnari 15-300C temperaturaze. nebismieri gamouyenebeli produqti an zedmeti masala unda ganikargos adgilobrivi moTxovnilebebis Sesabamisad. SeuTavsebloba intravenuri selsepti SeuTavsebelia intravenuri infuziis xsnarebTan garda deqstrozis intravenuri infuziisa. intravenuri selsepti ar unda airios an miRebul iqnas erTdroulad erTi da igive infuziis kaTetriT sxva intravenur wamlebTan an infuziis minarevebTan erTad. 4.3. SefuTva kafsulebi 250 mg 100, 300 tabletebi 500 mg 50, 150 ampulebi 500 mg 1, 5

wamali: SeinaxeT bavSvebisTvis miuwvdomel adgilas

TariRi: 2012 wlis oqtomberi kafsulebi, tabletebi damzadebulia : F. Hoffman –La Roche Ltd, Basel, Switzerland - Tvis Roche S.p.A. Milan-is mier, sawarmoo adgili Segrate, Italy ampulebi damzadebulia : F. Hoffman –La Roche Ltd, Basel, Switzerland - Tvis Roche Diagnostics GmbH-is mier, Mannheim, Germany

samedicino gamoyenebis instruqcia - roche.ge · pdf fileselseptis mimrebma pacientebma...

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