. . . . . . . . "N\u00ED\u017Ee jsou uvedeny ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky zaznamenan\u00E9 v klinick\u00FDch studi\u00EDch : \nHlavn\u00EDmi ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky hl\u00E1\u0161en\u00FDmi v souvislosti s pod\u00E1n\u00EDm mykofenol\u00E1t-mofetilu v kombinaci s cyklosporinem a kortikosteroidy jsou pr\u016Fjem, leukopenie, sepse a zvracen\u00ED. P\u0159i l\u00E9\u010Db\u011B p\u0159\u00EDpravkem Mycophenolate mofetil je tak\u00E9 pr\u016Fkazn\u011B zv\u00FD\u0161ena frekvence v\u00FDskytu n\u011Bkter\u00FDch druh\u016F infekc\u00ED (viz bod 4.4). \nMalignity: \nPacienti l\u00E9\u010Den\u00ED imunosupresivy v\u010Detn\u011B kombinac\u00ED l\u00E9\u010Div\u00FDch p\u0159\u00EDpravk\u016F zahrnuj\u00EDc\u00EDch Mycophenolate mofetil, jsou vystaveni zv\u00FD\u0161en\u00E9mu riziku v\u00FDskytu lymfom\u016F a dal\u0161\u00EDch malignit, p\u0159edev\u0161\u00EDm na k\u016F\u017Ei (viz bod 4.4). K rozvoji lymfoproliferativn\u00EDho onemocn\u011Bn\u00ED nebo lymfomu do\u0161lo u 0,6 % pacient\u016F u\u017E\u00EDvaj\u00EDc\u00EDch Mycophenolate mofetil (2 g nebo 3 g denn\u011B) v kombinaci s dal\u0161\u00EDmi imunosupresivy v kontrolovan\u00FDch klinick\u00FDch studi\u00EDch u pacient\u016F po transplantaci ledvin (d\u00E1vkov\u00E1n\u00ED 2 g denn\u011B), transplantaci srdce nebo jater p\u0159i sledov\u00E1n\u00ED nejm\u00E9n\u011B 1 rok. Karcinom k\u016F\u017Ee (krom\u011B melanomu) se objevil u 3,6 % pacient\u016F; jin\u00E9 typy malignit se objevily u 1,1 % pacient\u016F. \u00DAdaje o bezpe\u010Dnosti ze t\u0159\u00EDlet\u00E9ho sledov\u00E1n\u00ED u pacient\u016F po transplantaci ledvin nebo srdce neprok\u00E1zaly \u017E\u00E1dn\u00E9 neo\u010Dek\u00E1van\u00E9 zm\u011Bny incidence malignit ve srovn\u00E1n\u00ED s \u00FAdaji z ro\u010Dn\u00EDho sledov\u00E1n\u00ED. Pacienti po transplantaci jater byli sledov\u00E1ni d\u00E9le ne\u017E rok, ale m\u00E9n\u011B ne\u017E 3 roky. \nOportunn\u00ED infekce: \nV\u0161ichni pacienti po transplantaci jsou vystaveni vy\u0161\u0161\u00EDmu riziku vzniku oportunn\u00ED infekce, riziko se zvy\u0161uje s celkovou imunosupresivn\u00ED z\u00E1t\u011B\u017E\u00ED (viz bod 4.4). Nej\u010Dast\u011Bj\u0161\u00ED oportunn\u00ED infekce zaznamenan\u00E9 u pacient\u016F u\u017E\u00EDvaj\u00EDc\u00EDch Mycophenolate mofetil (2 g nebo 3 g denn\u011B) s dal\u0161\u00EDmi imunosupresivy v kontrolovan\u00FDch klinick\u00FDch studi\u00EDch u pacient\u016F po transplantaci ledvin (\u00FAdaje z d\u00E1vkov\u00E1n\u00ED 2 g denn\u011B), transplantaci srdce nebo jater p\u0159i sledov\u00E1n\u00ED po dobu nejm\u00E9n\u011B 1 roku byly kandid\u00F3za k\u016F\u017Ee a sliznic, CMV vir\u00E9mie/syndrom a herplex simplex. CMV vir\u00E9mie/syndrom byly zaznamen\u00E1ny u 13,5 % pacient\u016F. \nD\u011Bti a mladistv\u00ED (od 2 do 18 let): \nDruh a \u010Detnost v\u00FDskytu ne\u017E\u00E1douc\u00EDch \u00FA\u010Dink\u016F v klinick\u00E9 studii s 92 pacienty ve v\u011Bkov\u00E9m rozmez\u00ED od 2 do 18 let, kter\u00FDm bylo peror\u00E1ln\u011B pod\u00E1v\u00E1no 600 mg/m2 mykofenol\u00E1t-mofetilu dvakr\u00E1t denn\u011B, byly obecn\u011B podobn\u00E9 ne\u017E\u00E1douc\u00EDm \u00FA\u010Dink\u016Fm, kter\u00E9 byly zaznamen\u00E1ny u dosp\u011Bl\u00FDch pacient\u016F, kter\u00FDm byl pod\u00E1v\u00E1n Mycophenolate mofetil v d\u00E1vce 1 g dvakr\u00E1t denn\u011B. V\u00FDjimku tvo\u0159\u00ED d\u011Bt\u0161t\u00ED pacienti, p\u0159edev\u0161\u00EDm d\u011Bti mlad\u0161\u00ED 6 let, u kter\u00FDch byl \u010Dast\u011Bj\u0161\u00ED v\u00FDskyt pr\u016Fjmu, sepse, leukopenie, an\u00E9mie a infekce, ve srovn\u00E1n\u00ED s dosp\u011Bl\u00FDmi pacienty. \nStar\u0161\u00ED pacienti (\u2265 65 let): \nU star\u0161\u00EDch pacient\u016F (\u2265 65 let) je obecn\u011B zv\u00FD\u0161en\u00E9 riziko rozvoje ne\u017E\u00E1douc\u00EDch \u00FA\u010Dink\u016F v d\u016Fsledku imunosuprese. Star\u0161\u00ED pacienti, a to p\u0159edev\u0161\u00EDm ti, kte\u0159\u00ED u\u017E\u00EDvaj\u00ED Mycophenolate mofetil jako sou\u010D\u00E1st imunosupresivn\u00ED l\u00E9\u010Dby, jsou ve srovn\u00E1n\u00ED s mlad\u0161\u00EDmi pacienty vystaveni zv\u00FD\u0161en\u00E9mu riziku vzniku n\u011Bkter\u00FDch infekc\u00ED (v\u010Detn\u011B cytomegalovirov\u00FDch invazivn\u00EDch onemocn\u011Bn\u00ED tk\u00E1n\u00ED) a zv\u00FD\u0161en\u00E9mu riziku krv\u00E1cen\u00ED do za\u017E\u00EDvac\u00EDho traktu a plicn\u00EDho ed\u00E9mu. \nDal\u0161\u00ED ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky: \nNe\u017E\u00E1douc\u00ED \u00FA\u010Dinky vznikaj\u00EDc\u00ED v pravd\u011Bpodobn\u00E9 nebo mo\u017En\u00E9 souvislosti s l\u00E9\u010Dbou mykofenol\u00E1t mofetilem zaznamenan\u00E9 u \u2265 1/10 a u \u22651/100 a\u017E <1/10 pacient\u016F l\u00E9\u010Den\u00FDch mycofenol\u00E1t mofetilem v kontrolovan\u00FDch klinick\u00FDch studi\u00EDch u pacient\u016F po transplantaci ledvin (\u00FAdaje z d\u00E1vkov\u00E1n\u00ED 2 g denn\u011B), srdce nebo jater jsou uvedeny v n\u00E1sleduj\u00EDc\u00ED tabulce.\nNe\u017E\u00E1douc\u00ED \u00FA\u010Dinky v pravd\u011Bpodobn\u00E9 nebo mo\u017En\u00E9 souvislosti s l\u00E9\u010Dbou mykofenol\u00E1t- mofetilem v klinick\u00FDch studi\u00EDch hl\u00E1\u0161en\u00E9 u pacient\u016F po transplantaci ledvin, srdce nebo jater p\u0159i l\u00E9\u010Db\u011B mykofenol\u00E1t-mofetilem v kombinaci s cyklosporinem a kortikosteroidy\nV r\u00E1mci t\u0159\u00EDdy org\u00E1nov\u00FDch syst\u00E9m\u016F jsou ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky se\u0159azeny v rubrik\u00E1ch dle \u010Detnosti za pou\u017Eit\u00ED n\u00E1sleduj\u00EDc\u00EDch kategori\u00ED: velmi \u010Dast\u00E9 (\u22651/10); \u010Dast\u00E9 (\u22651/100 a\u017E <1/10); m\u00E9n\u011B \u010Dast\u00E9 (\u22651/1000 a\u017E <1/100); vz\u00E1cn\u00E9 (\u22651/10000 a\u017E <1/1000); velmi vz\u00E1cn\u00E9 (<1/10000), nezn\u00E1m\u00E9 (nen\u00ED mo\u017Eno odhadnout na z\u00E1klad\u011B dostupn\u00FDch dat).V ka\u017Ed\u00E9 skupin\u011B \u010Detnost\u00ED jsou ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky se\u0159azeny podle klesaj\u00EDc\u00ED z\u00E1va\u017Enosti.\n\tT\u0159\u00EDda org\u00E1nov\u00FDch syst\u00E9m\u016F\n\tNe\u017E\u00E1douc\u00ED \u00FA\u010Dinky l\u00E9\u010Div\u00E9ho p\u0159\u00EDpravku\n\tInfekce a infestace\n\tVelmi \u010Dast\u00E9\n\tSepse, gastrointestin\u00E1ln\u00ED kandid\u00F3za, infekce mo\u010Dov\u00FDch cest, herpes simplex, herpes zoster\n\t\n\t\u010Cast\u00E9\n\tPneumonie, ch\u0159ipka, infekce d\u00FDchac\u00EDch cest, respira\u010Dn\u00ED monili\u00E1za, gastrointestin\u00E1ln\u00ED infekce, kandid\u00F3za, gastroenteritida, infekce, bronchitida, faryngitida, sinusitida, pl\u00EDs\u0148ov\u00E1 onemocn\u011Bn\u00ED k\u016F\u017Ee, ko\u017En\u00ED kandida, vagin\u00E1ln\u00ED kandid\u00F3za, rinitida\n\tNovotvary benign\u00ED, malign\u00ED a bl\u00ED\u017Ee neur\u010Den\u00E9 (zahrnuj\u00EDc\u00ED cysty a polypy)\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tRakovina k\u016F\u017Ee, benign\u00ED ko\u017En\u00ED novotvar\n\tPoruchy krve a lymfatick\u00E9ho syst\u00E9mu\n\tVelmi \u010Dast\u00E9\n\tLeukopenie, trombocytopenie, an\u00E9mie\n\t\n\t\u010Cast\u00E9\n\tPancytopenie, leukocyt\u00F3za\n\tPoruchy metabolismu a v\u00FD\u017Eivy\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tAcid\u00F3za, hyperkal\u00E9mie, hypokal\u00E9mie, hyperglyk\u00E9mie, hypomagnez\u00E9mie, hypokalc\u00E9mie, hypercholesterol\u00E9mie, hyperlipid\u00E9mie, hypofosfat\u00E9mie, hyperurik\u00E9mie, dna, anorexie\n\tPsychiatrick\u00E9 poruchy\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tNeklid, zmatenost, deprese, \u00FAzkost, poruchy my\u0161len\u00ED, nespavost\n\tPoruchy nervov\u00E9ho syst\u00E9mu\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tK\u0159e\u010De, hypertonie, t\u0159es, somnolence, myastenick\u00FD syndrom, z\u00E1vrat\u011B, bolesti hlavy, parest\u00E9zie, dysgeuzie\n\tSrde\u010Dn\u00ED poruchy\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tTachykardie\n\tC\u00E9vn\u00ED poruchy\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tHypotenze, hypertenze, vasodilatace\n\tRespira\u010Dn\u00ED, hrudn\u00ED a mediastin\u00E1ln\u00ED poruchy\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tPleur\u00E1ln\u00ED v\u00FDpotek, dyspnoe, ka\u0161el\n\tGastrointestin\u00E1ln\u00ED poruchy\n\tVelmi \u010Dast\u00E9\n\tZvracen\u00ED, bolesti b\u0159icha, pr\u016Fjem, nauzea\n\t\n\t\u010Cast\u00E9\n\tKrv\u00E1cen\u00ED ze za\u017E\u00EDvac\u00EDho traktu, peritonitida, ileus, kolitida, \u017Ealude\u010Dn\u00ED v\u0159ed, duoden\u00E1ln\u00ED v\u0159ed, gastritida, ezofagitida, stomatitida, z\u00E1cpa, dyspepsie, flatulence, eruktace\n\tPoruchy jater a \u017Elu\u010Dov\u00FDch cest\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tHepatitida, \u017Eloutenka, hyperbilirubin\u00E9mie\n\tPoruchy k\u016F\u017Ee a podko\u017En\u00ED tk\u00E1n\u011B\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tHypertrofie k\u016F\u017Ee, vyr\u00E1\u017Eka, akn\u00E9, alopecie\n\tPoruchy svalov\u00E9 a kostern\u00ED soustavy a pojivov\u00E9 tk\u00E1n\u011B\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tArtralgie\n\tPoruchy ledvin a mo\u010Dov\u00FDch cest\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tZhor\u0161en\u00ED funkce ledvin\n\tCelkov\u00E9 poruchy a reakce v\u00A0m\u00EDst\u011B aplikace\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tOtok, pyrexie, zimnice, bolest, \u00FAnava, astenie\n\tVy\u0161et\u0159en\u00ED\n\tVelmi \u010Dast\u00E9\n\t-\n\t\n\t\u010Cast\u00E9\n\tZv\u00FD\u0161en\u00ED jatern\u00EDch enzym\u016F, zv\u00FD\u0161en\u00ED kreatininu v\u00A0krvi, zv\u00FD\u0161en\u00ED lakt\u00E1t-dehydrogen\u00E1zy v\u00A0krvi, zv\u00FD\u0161en\u00ED mo\u010Doviny v\u00A0krvi, zv\u00FD\u0161en\u00ED alkalick\u00E9 fosfat\u00E1zy v\u00A0krvi, \u00FAbytek v\u00E1hy\nPozn\u00E1mka: F\u00E1ze III klinick\u00E9ho hodnocen\u00ED prevence rejekce ren\u00E1ln\u00EDho, srde\u010Dn\u00EDho nebo jatern\u00EDho transplant\u00E1tu se \u00FA\u010Dastnilo 501 pacient\u016F (Mycophenolate mofetil 2g denn\u011B), 289 pacient\u016F (Mycophenolate mofetil 3,0 g denn\u011B), resp. 277 pacient\u016F (Mycophenolate mofetil 2,0 g i.v./3,0 g p. o. denn\u011B).\nD\u00E1le jsou uvedeny ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky zaznamenan\u00E9 v r\u00E1mci postmarketinkov\u00E9ho sledov\u00E1n\u00ED: \nNe\u017E\u00E1douc\u00ED \u00FA\u010Dinky hl\u00E1\u0161en\u00E9 v r\u00E1mci postmarketinkov\u00E9ho sledov\u00E1n\u00ED jsou podobn\u00E9 ne\u017E\u00E1douc\u00EDm \u00FA\u010Dink\u016Fm zaznamenan\u00FDm v kontrolovan\u00FDch studi\u00EDch u pacient\u016F po transplantaci ledvin, srdce nebo jater. Dal\u0161\u00ED ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky hl\u00E1\u0161en\u00E9 po uveden\u00ED p\u0159\u00EDpravku na trh jsou uvedeny n\u00ED\u017Ee s \u010Detnostmi, pokud jsou zn\u00E1my, uveden\u00FDmi v z\u00E1vork\u00E1ch.\nGastrointestin\u00E1ln\u00ED syst\u00E9m: gingiv\u00E1ln\u00ED hyperpl\u00E1zie (\u22651/100 a\u017E <1/10), kolitida v\u010Detn\u011B kolitidy vyvolan\u00E9 cytomegalovirem (\u22651/100 a\u017E <1/10), pankreatitida (\u22651/100 a\u017E <1/10) a p\u0159\u00EDpady intestin\u00E1ln\u00ED vil\u00F3zn\u00ED atrofie. \nOnemocn\u011Bn\u00ED v d\u016Fsledku imunosuprese: z\u00E1va\u017En\u00E9, \u017Eivot ohro\u017Euj\u00EDc\u00ED infekce jako meningitida, infek\u010Dn\u00ED endokarditida, tuberkul\u00F3za a atypick\u00E1 mykobakteri\u00E1ln\u00ED infekce. U pacient\u016F l\u00E9\u010Den\u00FDch imunosupresivy, v\u010Detn\u011B p\u0159\u00EDpravku Mycophenolate mofetil byly zaznamen\u00E1ny p\u0159\u00EDpady s BK virem asociovan\u00E9 nefropatie stejn\u011B jako p\u0159\u00EDpady s virem JC asociovan\u00E9 progresivn\u00ED multifok\u00E1ln\u00ED leukoencefalopatie (PML). \nByly hl\u00E1\u0161eny p\u0159\u00EDpady agranulocyt\u00F3zy (\u22651/1000 a\u017E <1/100) a neutrop\u00E9nie, proto je doporu\u010Dov\u00E1na pravideln\u00E1 kontrola pacient\u016F u\u017E\u00EDvaj\u00EDc\u00EDch p\u0159\u00EDpravek Mycophenolate mofetil (viz bod 4.4). U pacient\u016F l\u00E9\u010Den\u00FDch Mycophenolate mofetilem byly hl\u00E1\u0161eny p\u0159\u00EDpady v\u00FDskytu aplastick\u00E9 an\u00E9mie a \u00FAtlumu kostn\u00ED d\u0159en\u011B, n\u011Bkter\u00E9 z nich byly fat\u00E1ln\u00ED.\nPoruchy krve a lymfatick\u00E9ho syst\u00E9mu: U pacient\u016F l\u00E9\u010Den\u00FDch p\u0159\u00EDpravkem Mycophenolate mofetil byly zaznamen\u00E1ny p\u0159\u00EDpady \u010Dist\u00E9 aplazie \u010Derven\u00E9 \u0159ady (PRCA) (viz bod 4.4). \nOjedin\u011Bl\u00E9 p\u0159\u00EDpady abnorm\u00E1ln\u00ED morfologie neutrofil\u016F, v\u010Detn\u011B z\u00EDskan\u00E9 Pelger-Huetovy anom\u00E1lie, byly pozorov\u00E1ny u pacient\u016F l\u00E9\u010Den\u00FDch p\u0159\u00EDpravkem Mycophenolate mofetil. Tyto zm\u011Bny nejsou spojov\u00E1ny s poruchou funkce neutrofil\u016F. Tyto zm\u011Bny mohou p\u0159ipom\u00EDnat posun doleva (left shift) zralosti neutrofil\u016F p\u0159i hematologick\u00FDch vy\u0161et\u0159en\u00EDch, kter\u00E9 pak mohou b\u00FDt chybn\u011B interpretov\u00E1ny jako p\u0159\u00EDznaky infekce u imunosuprimova\u00FDch pacient\u016F, mezi n\u011B\u017E pat\u0159\u00ED i pacienti u\u017E\u00EDvaj\u00EDc\u00ED Mycophenolate mofetil. \nHypersensitivita: Byly hl\u00E1\u0161eny hypersensitivn\u00ED reakce v\u010Detn\u011B angioneurotick\u00E9ho ed\u00E9mu a anafylaktick\u00E9 reakce.\nKongenit\u00E1ln\u00ED poruchy: dal\u0161\u00ED informace viz bod 4.6. \nRespira\u010Dn\u00ED, hrudn\u00ED a mediastin\u00E1ln\u00ED poruchy: U pacient\u016F l\u00E9\u010Den\u00FDch p\u0159\u00EDpravkem Mycophenolate mofetil v kombinaci s dal\u0161\u00EDmi imunosupresivy byly ojedin\u011Ble hl\u00E1\u0161eny p\u0159\u00EDpady interstici\u00E1ln\u00EDho plicn\u00EDho onemocn\u011Bn\u00ED a plicn\u00ED fibr\u00F3zy, z nich\u017E n\u011Bkter\u00E9 byly fat\u00E1ln\u00ED.\n"@cs . . . . . . . . . . "004.008" . "4.8 Ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky "@cs . . . . . . . . . . . . . . . . . . . . . . . . . . .