. "\u00DA\u010Dinky v neklinick\u00FDch studi\u00EDch byly pozorov\u00E1ny pouze po expozic\u00EDch dostate\u010Dn\u011B p\u0159evy\u0161uj\u00EDc\u00EDch maxim\u00E1ln\u00ED expozici u \u010Dlov\u011Bka, co\u017E sv\u011Bd\u010D\u00ED o mal\u00E9m v\u00FDznamu p\u0159i klinick\u00E9m pou\u017Eit\u00ED. \nKarcinogeneze \nU my\u0161\u00ED a potkan\u016F l\u00E9\u010Den\u00FDch peror\u00E1ln\u011B po dobu 24 m\u011Bs\u00EDc\u016F d\u00E1vkami 2,5;5 nebo 10 mg/kg/den (p\u0159ibli\u017En\u011B 27x vy\u0161\u0161\u00EDmi d\u00E1vkami, ne\u017E jsou doporu\u010Den\u00E9 pro \u010Dlov\u011Bka) nebyl prok\u00E1z\u00E1n karcinogenn\u00ED potenci\u00E1l flukonazolu. U samc\u016F potkan\u016F l\u00E9\u010Den\u00FDch d\u00E1vkami 5 a 10 mg/kg/den byla zaznamen\u00E1na zv\u00FD\u0161en\u00E1 incidence hepatocelul\u00E1rn\u00EDho adenomu. \nReproduk\u010Dn\u00ED toxicita \nFlukonazol neovliv\u0148oval fertilitu samc\u016F a samic potkan\u016F l\u00E9\u010Den\u00FDch peror\u00E1ln\u00EDmi denn\u00EDmi d\u00E1vkami 5, 10 nebo 20 mg/kg nebo parenter\u00E1ln\u00EDmi d\u00E1vkami 5, 25 nebo 75 mg/kg. \nNebyly pops\u00E1ny \u017E\u00E1dn\u00E9 \u00FA\u010Dinky na plod p\u0159i d\u00E1vk\u00E1ch 5 nebo 10 mg/kg; zv\u00FD\u0161en\u00E1 \u010Detnost anatomick\u00FDch abnormalit u plodu (nadpo\u010Detn\u00E1 \u017Eebra, dilatace ledvinov\u00E9 p\u00E1nvi\u010Dky) a opo\u017Ed\u011Bn\u00E1 osifikace byly pozorov\u00E1ny p\u0159i d\u00E1vk\u00E1ch 25 a 50 mg/kg a vy\u0161\u0161\u00EDch. P\u0159i d\u00E1vk\u00E1ch v rozmez\u00ED od 80 mg/kg do 320 mg/kg byla popisov\u00E1na zv\u00FD\u0161en\u00E1 embryon\u00E1ln\u00ED letalita u potkan\u016F a abnormality plodu zahrnovaly zvln\u011Bn\u00E1 \u017Eebra, roz\u0161t\u011Bp patra a abnorm\u00E1ln\u00ED kraniofaci\u00E1ln\u00ED osifikace. \nP\u0159i peror\u00E1ln\u00EDch d\u00E1vk\u00E1ch 20 mg/kg se m\u00EDrn\u011B opo\u017E\u010Foval za\u010D\u00E1tek porodu a p\u0159i intraven\u00F3zn\u00EDch d\u00E1vk\u00E1ch od 20 mg/kg do 40 mg/kg byly u n\u011Bkolika samic pozorov\u00E1ny funk\u010Dn\u00ED poruchy d\u011Blo\u017En\u00EDch kontrakc\u00ED a prodlou\u017Een\u00ED porodu. Porodn\u00ED poruchy zp\u016Fsobily m\u00EDrn\u00FD n\u00E1r\u016Fst po\u010Dtu mrtv\u011B narozen\u00FDch ml\u00E1\u010Fat a sn\u00ED\u017Een\u00ED m\u00EDry p\u0159e\u017Eit\u00ED novorozen\u00FDch ml\u00E1\u010Fat p\u0159i t\u011Bchto d\u00E1vk\u00E1ch. Ovlivn\u011Bn\u00ED porodu potkan\u016F souvis\u00ED s druhov\u011B specifick\u00FDm sn\u00ED\u017Een\u00EDm estrogen\u016F jako n\u00E1sledku vysok\u00FDch d\u00E1vek flukonazolu. Obdobn\u00E9 hormon\u00E1ln\u00ED zm\u011Bny u \u017Een u\u017E\u00EDvaj\u00EDc\u00EDch flukonazol nebyly pozorov\u00E1ny (viz bod 5.1). \t \n"@cs . . . . . . "005.003" . . "\uFFFD 5.3 P\u0159edklinick\u00E9 \u00FAdaje vztahuj\u00EDc\u00ED se k bezpe\u010Dnosti "@cs .