. . . . . . . . . . . . . . . . . . . . . . . . . . "4.6 T\u011Bhotenstv\u00ED a kojen\u00ED\uFFFD"@cs . . . "004.006" . . "T\u011Bhotenstv\u00ED\nExperimenty na hlodavc\u00EDch dost\u00E1vaj\u00EDc\u00EDch vysok\u00E9 d\u00E1vky rifampicinu prok\u00E1zaly teratogenn\u00ED \u00FA\u010Dinky l\u00E9ku. Vzhledem k nedostatku dostate\u010Dn\u011B \u010Detn\u00FDch a kontrolovan\u00FDch studi\u00ED u t\u011Bhotn\u00FDch \u017Een m\u016F\u017Ee b\u00FDt rifampicin pod\u00E1v\u00E1n t\u011Bhotn\u00FDm \u017Een\u00E1m jen tehdy, je-li jistota, \u017Ee tuberkul\u00F3zn\u00ED proces je aktivn\u00ED a p\u0159\u00EDnos pro matku p\u0159eva\u017Euje nad potencion\u00E1ln\u00EDm rizikem ohro\u017Een\u00ED plodu. \nRifampicin u\u017E\u00EDvan\u00FD v posledn\u00EDch m\u011Bs\u00EDc\u00EDch t\u011Bhotenstv\u00ED m\u016F\u017Ee zp\u016Fsobit poporodn\u00ED krv\u00E1cen\u00ED u matky i novorozence. V takov\u00FDch p\u0159\u00EDpadech m\u016F\u017Ee b\u00FDt indikov\u00E1no pod\u00E1v\u00E1n\u00ED vitaminu K. \nKojen\u00ED\nRifampicin p\u0159ech\u00E1z\u00ED do mate\u0159sk\u00E9ho ml\u00E9ka. Koj\u00EDc\u00EDm \u017Een\u00E1m m\u016F\u017Ee b\u00FDt rifampicin pod\u00E1v\u00E1n jen po d\u016Fkladn\u00E9m zv\u00E1\u017Een\u00ED (l\u00E9ka\u0159em) pom\u011Bru l\u00E9\u010Debn\u00E9ho prosp\u011Bchu pro matku a rizika pro d\u00EDt\u011B. \n4.7 \u00DA\u010Dinky na schopnost \u0159\u00EDdit a obsluhovat stroje\uFFFD Nedostatek \u00FAdaj\u016F ohledn\u011B vlivu p\u0159\u00EDpravku na schopnost \u0159\u00EDdit vozidla a obsluhovat stroje. \uFFFD\uFFFD\n4.8 Ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky\uFFFD Vzhledem k nedostatku \u00FAdaj\u016F o frekvenci v\u00FDskytu n\u00ED\u017Ee uveden\u00FDch ne\u017E\u00E1douc\u00EDch \u00FA\u010Dink\u016F, jsou ne\u017E\u00E1douc\u00ED \u00FA\u010Dinky za\u0159azeny do t\u0159\u00EDd org\u00E1nov\u00FDch syst\u00E9m\u016F podle MedDRA.\nPoruchy krve a lymfatick\u00E9ho syst\u00E9mu: akutn\u00ED hemolytick\u00E1 an\u00E9mie. \nM\u016F\u017Ee se vyskytnout trombocytopenie s purpurou nebo bez n\u00ED, obvykle spojen\u00E1 s p\u0159eru\u0161ovanou l\u00E9\u010Dbou, ale je reverzibiln\u00ED, pokud se l\u00E9\u010Dba ukon\u010D\u00ED ihned, jakmile se purpura objev\u00ED. \nPokud l\u00E9\u010Dba rifampicinem pokra\u010Dovala po v\u00FDskytu purpury, do\u0161lo ke krv\u00E1cen\u00ED do mozku a \u00FAmrt\u00ED. \nVelmi vz\u00E1cn\u011B se objevila agranulocyt\u00F3za. \nVz\u00E1cn\u011B byla hl\u00E1\u0161ena roztrou\u0161en\u00E1 intravaskul\u00E1rn\u00ED koagulace. \nU mal\u00E9ho procenta pacient\u016F se objevila eosinofilie a leukopenie.\nPoruchy imunitn\u00EDho syst\u00E9mu: anafylaxe. U mal\u00E9ho procenta pacient\u016F l\u00E9\u010Den\u00FDch rifampicinem se objevila eosinofilie, leukopenie a ed\u00E9m. \n\"Ch\u0159ipkov\u00FD syndrom\" zahrnuj\u00EDc\u00ED epizody hore\u010Dky, zimnice, bolesti hlavy, z\u00E1vrat\u00ED a bolesti kost\u00ED se objevoval nej\u010Dast\u011Bji v pr\u016Fb\u011Bhu 3. a\u017E 6. m\u011Bs\u00EDce l\u00E9\u010Dby. \u010Cetnost syndromu se li\u0161\u00ED, ale m\u016F\u017Ee se vyskytnout a\u017E u 50% pacient\u016F, kte\u0159\u00ED dost\u00E1vali jednou t\u00FDdn\u011B d\u00E1vku rifampicinu 25 mg/kg nebo v\u00EDce . \nPoruchy nervov\u00E9ho syst\u00E9mu: Vz\u00E1cn\u011B byly hl\u00E1\u0161eny psych\u00F3zy. \nC\u00E9vn\u00ED poruchy: pokles krevn\u00EDho tlaku a \u0161ok. \nRespira\u010Dn\u00ED, hrudn\u00ED a mediastin\u00E1ln\u00ED poruchy: du\u0161nost a s\u00EDp\u00E1n\u00ED.\nGastrointestin\u00E1ln\u00ED poruchy: nechutenstv\u00ED, nauzea, zvracen\u00ED, bolesti b\u0159icha a pr\u016Fjem. \nP\u0159i l\u00E9\u010Db\u011B rifampicinem byla zaznamen\u00E1na pseudomembran\u00F3zn\u00ED kolitida. \nHepatobili\u00E1rn\u00ED poruchy: rifampicin m\u016F\u017Ee zp\u016Fsobit hepatitidu, a proto je t\u0159eba sledovat jatern\u00ED testy (viz bod 4.4. Zvl\u00E1\u0161tn\u00ED upozorn\u011Bn\u00ED a opat\u0159en\u00ED pro pou\u017Eit\u00ED). \nPoruchy k\u016F\u017Ee a podko\u017En\u00ED tk\u00E1n\u011B jsou m\u00EDrn\u00E9 a samy vymiz\u00ED, a nezd\u00E1 se, \u017Ee to jsou reakce z p\u0159ecitliv\u011Blosti. \nObvykle se jedn\u00E1 o zarudnut\u00ED a sv\u011Bd\u011Bn\u00ED, s vyr\u00E1\u017Ekou nebo bez n\u00ED. Objevila se kop\u0159ivka a z\u00E1va\u017En\u011Bj\u0161\u00ED ko\u017En\u00ED reakce z p\u0159ecitliv\u011Blosti, ale jsou m\u00E9n\u011B \u010Dast\u00E9. Vz\u00E1cn\u011B byla hl\u00E1\u0161ena exfoliativn\u00ED dermatitida, pemfigoidn\u00ED reakce, erythema multiforme v\u010Detn\u011B Stevens-Johnsonova syndromu, Lyellsova syndromu a vaskulitida. \nPoruchy svalov\u00E9 a kostern\u00ED soustavy a pojivov\u00E9 tk\u00E1n\u011B: U mal\u00E9ho procenta pacient\u016F l\u00E9\u010Den\u00FDch rifampicinem se objevila svalov\u00E1 slabost a myopatie.\nPoruchy ledvin a mo\u010Dov\u00FDch cest: akutn\u00ED selh\u00E1n\u00ED ledvin obvykle v d\u016Fsledku akutn\u00ED tubul\u00E1rn\u00ED nekr\u00F3zy nebo akutn\u00ED interstici\u00E1ln\u00ED nefritidy. \nEndokrinn\u00ED poruchy: Vz\u00E1cn\u011B byla hl\u00E1\u0161ena nedostate\u010Dnost nadledvin u\u00A0pacient\u016F s poruchou funkce nadledvin. \nPoruchy reproduk\u010Dn\u00EDho syst\u00E9mu a prsu: p\u0159i dlouhodob\u00E9 antituberkul\u00F3zn\u00ED terapii obsahuj\u00EDc\u00ED rifampicin byly hl\u00E1\u0161eny ob\u010Dasn\u00E9 poruchy menstrua\u010Dn\u00EDho cyklu. \nRifampicin m\u016F\u017Ee zp\u016Fsobit \u010Derven\u00E9 zabarven\u00ED mo\u010Di, sputa a slz. Pacienta je nutn\u00E9 o tom p\u0159edem informovat. \nM\u011Bkk\u00E9 kontaktn\u00ED \u010Do\u010Dky mohou b\u00FDt trvale zabarveny.\nPokud se objev\u00ED z\u00E1va\u017En\u00E9 komplikace, jako je nap\u0159. ren\u00E1ln\u00ED selh\u00E1n\u00ED, trombocytopenie nebo hemolytick\u00E1 an\u00E9mie, l\u00E9\u010Dba rifampicinem mus\u00ED b\u00FDt zcela ukon\u010Dena . \n4.9 P\u0159ed\u00E1vkov\u00E1n\u00ED\uFFFD\uFFFD Brzy po p\u0159ed\u00E1vkov\u00E1n\u00ED rifampcinem se mohou objevit nauzea, zvracen\u00ED, \u017Eloutenka, poruchy v\u011Bdom\u00ED a\u017E bezv\u011Bdom\u00ED p\u0159i akutn\u00ED jatern\u00ED insuficienci. \uFFFDV p\u0159\u00EDpad\u011B otravy rifampicinem je na m\u00EDst\u011B co nejrychleji odstranit z organismu je\u0161t\u011B nevst\u0159ebanou l\u00E9\u010Divou l\u00E1tku (vyvol\u00E1n\u00ED zvracen\u00ED, v\u00FDplach \u017Ealudku) nebo zm\u00EDrnit jej\u00ED vst\u0159eb\u00E1v\u00E1n\u00ED z tr\u00E1vic\u00EDho traktu (pod\u00E1n\u00ED aktivn\u00EDho uhl\u00ED), je-li pacient p\u0159i v\u011Bdom\u00ED. \uFFFDL\u00E9\u010Dba otravy je p\u0159edev\u0161\u00EDm symptomatick\u00E1 a spo\u010D\u00EDv\u00E1 v monitorov\u00E1n\u00ED a podpo\u0159e z\u00E1kladn\u00EDch \u017Eivotn\u00EDch funkc\u00ED. Rifampicin je mo\u017En\u00E9 odstranit z organismu hemodial\u00FDzou. \uFFFD\uFFFD\uFFFD 5. FARMAKOLOGICK\u00C9 VLASTNOSTI\uFFFD\uFFFD5.1 Farmakodynamick\u00E9 vlastnosti\uFFFD\uFFFDFarmakoterapeutick\u00E1 skupina: antimykobakteri\u00E1ln\u00ED l\u00E9\u010Diva, l\u00E9\u010Diva k\u00A0terapii tuberkul\u00F3zy (tuberkulostatika)\nATC k\u00F3d: J04AB02\uFFFD\uFFFDRifampicin je ansamycinov\u00E9 antibiotikum. Je polosyntetick\u00FDm deriv\u00E1tem rifamicinu B, vytv\u00E1\u0159en\u00E9ho Streptomyces mediterranei. Rifampicin p\u016Fsob\u00ED baktericidn\u011B tak, \u017Ee blokuje aktivitu DNA-dependentn\u00ED RNA polymer\u00E1zy. P\u016Fsob\u00ED siln\u011B baktericidn\u011B na mykobakteria tuberkul\u00F3zy, atypick\u00E1 mykobakteria a mykobakteria lepry. V podm\u00EDnk\u00E1ch in vitro\u00A0 tak\u00E9 inhibuje r\u016Fst grampozitivn\u00EDch mikrob\u016F (hlavn\u011B stafylokok\u016F, nap\u0159. Staphylococcus aureus, Staphylococcus epidermidis) a Gram-negativn\u00EDch mikrob\u016F (nap\u0159. Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Legionella spp.). \nB\u011Bhem l\u00E9\u010Dby rifampicinem doch\u00E1z\u00ED k selekci rezistentn\u00EDch kmen\u016F, m\u00E1 se proto pod\u00E1vat po stanoven\u00ED citlivosti, kr\u00E1tce a v\u00A0kombinaci s\u00A0jin\u00FDmi antibiotiky, aby se rezistenci p\u0159ede\u0161lo. \uFFFD\uFFFD\uFFFD 5.2 Farmakokinetick\u00E9 vlastnosti\nRifampicin podan\u00FD peror\u00E1ln\u011B se rychle vst\u0159eb\u00E1v\u00E1 z tr\u00E1vic\u00EDho \u00FAstroj\u00ED, t\u00E9m\u011B\u0159 100%. Obsah potravy v \u017Ealudku zna\u010Dn\u011B omezuje jeho vst\u0159eb\u00E1v\u00E1n\u00ED. \uFFFDS b\u00EDlkovinami se v\u00E1\u017Ee asi ze 75%, polo\u010Das vylu\u010Dov\u00E1n\u00ED je 2 a\u017E 5 hodin. Po peror\u00E1ln\u00EDm pod\u00E1n\u00ED 600 mg rifampicinu je biologick\u00FD polo\u010Das zhruba 3 hodiny, zat\u00EDmco po pod\u00E1n\u00ED 900 mg vzr\u016Fst\u00E1 na zhruba 5 hodin. Rifampicin podan\u00FD peror\u00E1ln\u011B v d\u00E1vce 10 mg/kg t.hm. dosahuje po zhruba 2 \u2013 4 hodin\u00E1ch maxim\u00E1ln\u00ED koncentrace v krvi zhruba 10 \u03BCg/ml.\uFFFDRifampicin dob\u0159e pronik\u00E1 do tuberkul\u00F3zn\u00EDch lo\u017Eisek, lymfatick\u00FDch uzlin a t\u011Bln\u00EDch tekutin. Proch\u00E1z\u00ED placentou i do mate\u0159sk\u00E9ho ml\u00E9ka. V mozkom\u00ED\u0161n\u00EDm moku dosahuje l\u00E9\u010Debn\u00FDch hladin u z\u00E1n\u011Btliv\u00FDch stav\u016F. \nRifampicin se metabolizuje v j\u00E1trech. \nP\u0159ibli\u017En\u011B 60% peror\u00E1ln\u011B p\u0159ijat\u00E9 d\u00E1vky je vylu\u010Dov\u00E1no stolic\u00ED a 30% mo\u010D\u00ED. Nevelk\u00FD pod\u00EDl l\u00E9\u010Diva je vylou\u010Den slzami, potem a jin\u00FDmi t\u011Bln\u00EDmi tekutinami, kter\u00E9 se zbarvuj\u00ED do oran\u017Eova. Jatern\u00ED insuficience je indikac\u00ED ke sn\u00ED\u017Een\u00ED d\u00E1vek p\u0159\u00EDpravku, zat\u00EDmco p\u0159i nedostate\u010Dnosti ledvin m\u016F\u017Ee b\u00FDt pln\u00E9 d\u00E1vkov\u00E1n\u00ED zachov\u00E1no. \uFFFD\n\uFFFD\uFFFD 5.3 P\u0159edklinick\u00E9 \u00FAdaje vztahuj\u00EDc\u00ED se k bezpe\u010Dnosti \uFFFD \uFFFD U lid\u00ED nebyly provedeny dlouhodob\u00E9 studie potenci\u00E1ln\u00EDho mutagenn\u00EDho, kancerogenn\u00EDho a teratogenn\u00EDho \u00FA\u010Dinku rifampicinu.\nPotenci\u00E1ln\u00ED kancerogenn\u00ED \u00FA\u010Dinek rifampicinu byl zji\u0161t\u011Bn u samic i samc\u016F my\u0161\u00ED poch\u00E1zej\u00EDch z r\u016Fzn\u00FDch kmen\u016F. Zv\u00ED\u0159at\u016Fm byl rifampicin pod\u00E1v\u00E1n peror\u00E1ln\u011B po dobu 60 t\u00FDdn\u016F v d\u00E1vk\u00E1ch 2-10kr\u00E1t vy\u0161\u0161\u00EDch ne\u017E jsou pr\u016Fm\u011Brn\u00E9 d\u00E1vky u \u010Dlov\u011Bka. N\u00E1r\u016Fst incidence n\u00E1dor\u016F jater byl prok\u00E1z\u00E1n jen u samic t\u011Bch my\u0161\u00ED, kter\u00E9 poch\u00E1zely z kmene charakterizovan\u00E9ho zvl\u00E1\u0161tn\u00ED n\u00E1chylnost\u00ED ke spont\u00E1nn\u00EDmu vzniku n\u00E1dor\u016F. U samc\u016F my\u0161\u00ED t\u00E9ho\u017E kmene a u samc\u016F a samic my\u0161\u00ED jin\u00FDch kmen\u016F nebyly pozorov\u00E1ny p\u0159\u00EDpady v\u00FDskytu \u017E\u00E1dn\u00FDch n\u00E1dor\u016F.\nTeratogenn\u00ED \u00FA\u010Dinek rifampicinu byl pozorov\u00E1n u hlodavc\u016F, kter\u00FDm se peror\u00E1ln\u011B pod\u00E1val p\u0159\u00EDpravek v d\u00E1vk\u00E1ch 15-25kr\u00E1t vy\u0161\u0161\u00EDch ne\u017E jsou pr\u016Fm\u011Brn\u00E9 d\u00E1vky pro \u010Dlov\u011Bka.\n6. FARMACEUTICK\u00C9 \u00DADAJE\uFFFD6.1 Seznam pomocn\u00FDch l\u00E1tek\uFFFD\tObsah tobolky: mastek, magnesium-stear\u00E1t, natrium-lauryl-sulf\u00E1t.\uFFFD\tV\u00ED\u010Dko a t\u011Blo tobolky: : \u017Eelatina, oxid titani\u010Dit\u00FD (E171), \u010Derven\u00FD oxid \u017Eelezit\u00FD (E172).\n6.2 Inkompatibility\uFFFD Neuplat\u0148uje se. \uFFFD\uFFFD 6.3 Doba pou\u017Eitelnosti\n3 roky\uFFFD\uFFFD 6.4 Zvl\u00E1\u0161tn\u00ED opat\u0159en\u00ED pro uchov\u00E1v\u00E1n\u00ED\uFFFD Uchov\u00E1vejte p\u0159i teplot\u011B do 25\u00BAC v dob\u0159e uzav\u0159en\u00E9m p\u016Fvodn\u00EDm obalu, aby byl l\u00E9\u010Div\u00FD p\u0159\u00EDpravek chr\u00E1n\u011Bn p\u0159ed sv\u011Btlem a vlhkost\u00ED. \uFFFDUchov\u00E1vejte mimo dosah a dohled d\u011Bt\u00ED. \uFFFD\uFFFD\uFFFD 6.5 Druh obalu a velikost balen\u00ED\uFFFD\uFFFD BENEMICIN 150 mg i BENEMICIN 300 mg\uFFFD\tb\u00EDl\u00E1 PP n\u00E1dobka s\u00A0HDPE pojistn\u00FDm uz\u00E1v\u011Brem a krabi\u010Dka.\nVelikost balen\u00ED: \t100 x 150 mg\uFFFD\t\t\t100 x 300 mg\n6.6 Zvl\u00E1\u0161tn\u00ED opat\u0159en\u00ED pro likvidaci p\u0159\u00EDpravku a pro zach\u00E1zen\u00ED s n\u00EDm\uFFFD V\u0161echen nepou\u017Eit\u00FD p\u0159\u00EDpravek mus\u00ED b\u00FDt zlikvidov\u00E1n v souladu se z\u00E1sadami likvidace nebezpe\u010Dn\u00E9ho odpadu.\n"@cs . . . . . . . . . . . .