. . . . . . . . . . . . . . . . . . . . . . "Riziko myopatie p\u0159i l\u00E9\u010Db\u011B inhibitory HMG-CoA redukt\u00E1zy je zv\u00FD\u0161en\u00E9 p\u0159i sou\u010Dasn\u00E9m pod\u00E1v\u00E1n\u00ED cyklosporinu, fibr\u00E1t\u016F, makrolidov\u00FDch antibiotik v\u010Detn\u011B erytromycinu, antimykotik azolov\u00E9ho typu, inhibitor\u016F HIV prote\u00E1zy nebo deriv\u00E1t\u016F kyseliny nikotinov\u00E9 (niacinu), p\u0159i\u010Dem\u017E se vz\u00E1cn\u011B objevila rabdomyol\u00FDza s poruchou funkce ledvin jako n\u00E1sledek myoglobinurie. V p\u0159\u00EDpadech, kde je nezbytn\u00E9 sou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED t\u011Bchto l\u00E9k\u016F s atorvastatinem, je t\u0159eba pe\u010Dliv\u011B zv\u00E1\u017Eit p\u0159\u00EDnos a riziko soub\u011B\u017En\u00E9 l\u00E9\u010Dby. Pokud pacienti u\u017E\u00EDvaj\u00ED l\u00E9ky, kter\u00E9 zvy\u0161uj\u00ED plazmatickou koncentraci atorvastatinu, jsou doporu\u010Deny ni\u017E\u0161\u00ED po\u010D\u00E1te\u010Dn\u00ED d\u00E1vky atorvastatinu. V p\u0159\u00EDpad\u011B cyklosporinu, klaritromycinu a itrakonazolu by m\u011Bla b\u00FDt zv\u00E1\u017Eena ni\u017E\u0161\u00ED maxim\u00E1ln\u00ED d\u00E1vka atorvastatinu a je doporu\u010Deno pe\u010Dliv\u00E9 klinick\u00E9 sledov\u00E1n\u00ED t\u011Bchto pacient\u016F (viz bod 4.4).\nInhibitory cytochromu P 450 3A4\nAtorvastatin je metabolizov\u00E1n cytochromem P 450 3A4. M\u016F\u017Ee doj\u00EDt k interakci, je-li p\u0159\u00EDpravek AMEDO pod\u00E1v\u00E1n spolu s inhibitory cytochromu P 450 3A4 (nap\u0159. cyklosporin, makrolidov\u00E1 antibiotika v\u010Detn\u011B erytromycinu a klaritromycinu, nefazodonu, antimykotika azolov\u00E9ho typu v\u010Detn\u011B itrakonazolu a inhibitor\u016F HIV prote\u00E1z). Soub\u011B\u017En\u00E9 pod\u00E1n\u00ED m\u016F\u017Ee v\u00E9st k zv\u00FD\u0161en\u00FDm plazmatick\u00FDm koncentrac\u00EDm atorvastatinu. Je t\u0159eba zvl\u00E1\u0161tn\u00ED opatrnosti p\u0159i kombinov\u00E1n\u00ED atorvastatinu s t\u011Bmito l\u00E9\u010Div\u00FDmi l\u00E1tkami (viz bod 4.4).\nInhibitory transportn\u00EDch protein\u016F\nAtorvastatin a jeho metabolity jsou substr\u00E1ty OATP1B1 transport\u00E9r\u016F. Sou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED atorvastatinu 10 mg a cyklosporinu 5,2 mg/kg/den vedlo k 7,7 n\u00E1sobn\u00E9mu zv\u00FD\u0161en\u00ED expozice atorvastatinu. V p\u0159\u00EDpadech, kde je sou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED atorvastatinu s cyklosporinem nezbytn\u00E9, d\u00E1vka atorvastatinu by nem\u011Bla p\u0159ekro\u010Dit 10 mg.\nErytromycin, klaritromycin\nErytromycin a klaritromycin jsou zn\u00E1m\u00E9 inhibitory cytochromu P450 3A4. Sou\u010Dasn\u00E9 u\u017E\u00EDv\u00E1n\u00ED atorvastatinu 80 mg 1x denn\u011B a erytromycinu (500 mg 4x denn\u011B) vedlo k\u00A033% zv\u00FD\u0161en\u00ED expozice celkov\u00E9 aktivity atorvastatinu. Sou\u010Dasn\u00E9 u\u017E\u00EDv\u00E1n\u00ED atorvastatinu 10 mg 1x denn\u011B a klaritromycinu (500 mg 2x denn\u011B), zn\u00E1m\u00FDch inhibitor\u016F cytochromu P450 3A4, vedlo k 3,4 n\u00E1sobn\u00E9mu zv\u00FD\u0161en\u00ED expozice atorvastatinu. V p\u0159\u00EDpadech, kdy je sou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED klaritromycinu s atorvastatinem nezbytn\u00E9, jsou doporu\u010Deny ni\u017E\u0161\u00ED udr\u017Eovac\u00ED d\u00E1vky atorvastatinu. P\u0159i d\u00E1vk\u00E1ch atorvastatinu p\u0159evy\u0161uj\u00EDc\u00EDch 40 mg se doporu\u010Duje pe\u010Dliv\u00E9 sledov\u00E1n\u00ED t\u011Bchto pacient\u016F.\nItrakonazol\nSoub\u011B\u017En\u00E9 pod\u00E1n\u00ED atorvastatinu 20-40 mg a itrakonazolu 200 mg denn\u011B vedlo k 1,5-2,3n\u00E1sobn\u00E9mu zv\u00FD\u0161en\u00ED expozice atorvastatinu. V p\u0159\u00EDpadech, kdy je sou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED itrakonazolu s atorvastatinem nezbytn\u00E9, jsou doporu\u010Deny ni\u017E\u0161\u00ED udr\u017Eovac\u00ED d\u00E1vky atorvastatinu. P\u0159i d\u00E1vk\u00E1ch atorvastatinu p\u0159evy\u0161uj\u00EDc\u00EDch 40 mg se doporu\u010Duje pe\u010Dliv\u00E9 klinick\u00E9 sledov\u00E1n\u00ED t\u011Bchto pacient\u016F.\nInhibitory prote\u00E1z\nSoub\u011B\u017En\u00E9 pod\u00E1n\u00ED atorvastatinu a inhibitor\u016F prote\u00E1z, zn\u00E1m\u00FDch inhibitor\u016F cytochromu P 450 3A4, bylo spojeno se zv\u00FD\u0161en\u00EDm plazmatick\u00FDch hladin atorvastatinu.\nDiltiazem hydrochlorid\nSoub\u011B\u017En\u00E9 pod\u00E1v\u00E1n\u00ED diltiazemu 240 mg s atorvastatinem 40 mg vedlo k 51% zv\u00FD\u0161en\u00ED expozice atorvastatinu. Po zah\u00E1jen\u00ED pod\u00E1v\u00E1n\u00ED diltiazemu nebo n\u00E1sledn\u011B po \u00FAprav\u011B jeho d\u00E1vky se doporu\u010Duje pe\u010Dliv\u00E9 klinick\u00E9 sledov\u00E1n\u00ED t\u011Bchto pacient\u016F.\nEzetimib\nPod\u00E1v\u00E1n\u00ED samotn\u00E9ho ezetimibu je spojov\u00E1no s myopati\u00ED. Riziko myopatie m\u016F\u017Ee b\u00FDt proto zv\u00FD\u0161eno p\u0159i soub\u011B\u017En\u00E9m pod\u00E1v\u00E1n\u00ED ezetimibu a atorvastatinu.\nGrepfruitov\u00E1 \u0161\u0165\u00E1va\nObsahuje jednu nebo v\u00EDce slo\u017Eek, kter\u00E9 inhibuj\u00ED CYP3A4 a mohou zv\u00FD\u0161it plazmatick\u00E9 koncentrace l\u00E1tek metabolizovan\u00FDch CYP3A4. P\u0159\u00EDjem 240 ml skleni\u010Dky grepfruitov\u00E9 \u0161\u0165\u00E1vy vedl v n\u00E1r\u016Fstu AUC atorvastatinu o 37% a sn\u00ED\u017Een\u00ED AUC \u00FA\u010Dinn\u00E9ho ortohydroxy-metabolitu o 20,4%. V\u011Bt\u0161\u00ED mno\u017Estv\u00ED grepfruitov\u00E9 \u0161\u0165\u00E1vy (v\u00EDce ne\u017E 1,2 litru denn\u011B v pr\u016Fb\u011Bhu 5 dn\u00ED) zv\u00FD\u0161ilo AUC atorvastatinu 2,5x a AUC aktivn\u00ED HMG-CoA redukt\u00E1zy inhibitor\u016F (atorvastatinu a metabolit\u016F) 1,3x. Sou\u010Dasn\u00FD p\u0159\u00EDjem velk\u00E9ho mno\u017Estv\u00ED atorvastatinu a grepfruitov\u00E9 \u0161\u0165\u00E1vy nen\u00ED proto doporu\u010Dov\u00E1n.\nInduktory cytochromu P 450 3A4\nSou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED atorvastatinu s induktory cytochromu P450 3A (nap\u0159. efavirenz, rifampin, t\u0159ezalka te\u010Dkovan\u00E1) m\u016F\u017Ee v\u00E9st k prom\u011Bnliv\u00FDm sn\u00ED\u017Een\u00EDm plazmatick\u00FDch koncentrac\u00ED atorvastatinu. S ohledem na du\u00E1ln\u00ED mechanizmus interakce rifampinu (indukce cytochromu P450 3A a inhibice transport\u00E9ru OATP1B1 jatern\u00ED bu\u0148ky), se doporu\u010Duje p\u0159i soub\u011B\u017En\u00E9 pod\u00E1v\u00E1n\u00ED atorvastatinu s rifampinem pod\u00E1n\u00ED obou l\u00E9\u010Div\u00FDch p\u0159\u00EDpravk\u016F sou\u010Dasn\u011B, proto\u017Ee pod\u00E1n\u00ED atorvastatinu opo\u017Ed\u011Bn\u011B za pod\u00E1n\u00EDm rifampinu m\u016F\u017Ee b\u00FDt spojeno s v\u00FDznamn\u00FDm sn\u00ED\u017Een\u00EDm plazmatick\u00FDch koncentrac\u00ED atorvastatinu.\nVerapamil a amiodaron\nInterak\u010Dn\u00ED studie s verapamilem a amiodaronem nebyly prov\u00E1d\u011Bny. Jak verapamil tak amiodaron jsou zn\u00E1m\u00E9 inhibic\u00ED aktivity CYP3A4 a soub\u011B\u017En\u00E9 pod\u00E1v\u00E1n\u00ED s atorvastatinem m\u016F\u017Ee v\u00E9st ke zv\u00FD\u0161en\u00E9 expozici atorvastatinu.\nJin\u00E1 soub\u011B\u017En\u00E1 l\u00E9\u010Dba\nGemfibrozil / fibr\u00E1ty\nPou\u017Eit\u00ED fibr\u00E1t\u016F samotn\u00FDch je ob\u010Das spojov\u00E1no s myopati\u00ED. Riziko myopatie zp\u016Fsoben\u00E9 atorvastatinem m\u016F\u017Ee b\u00FDt vy\u0161\u0161\u00ED za sou\u010Dasn\u00E9ho u\u017E\u00EDv\u00E1n\u00ED fibr\u00E1t\u016F (viz bod 4.4). Sou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED gemfibrozilu 600 mg 2x denn\u011B vedlo k 24% zv\u00FD\u0161en\u00ED expozice atorvastatinu.\nDigoxin\nSou\u010Dasn\u00E9 opakovan\u00E9 u\u017E\u00EDv\u00E1n\u00ED digoxinu a atorvastatinu v d\u00E1vce 10 mg nezm\u011Bnilo plazmatickou koncentraci digoxinu v rovnov\u00E1\u017En\u00E9m stavu. Av\u0161ak koncentrace digoxinu se zv\u00FD\u0161ila o cca 20% p\u0159i sou\u010Dasn\u00E9m pod\u00E1v\u00E1n\u00ED digoxinu a 80 mg atorvastatinu 1x denn\u011B. Tuto interakci je mo\u017En\u00E9 vysv\u011Btlit inhibic\u00ED membr\u00E1nov\u00E9ho transportn\u00EDho proteinu, P-glykoproteinu. Je nutn\u00E9 kontrolovat pacienty l\u00E9\u010Den\u00E9 digoxinem.\nPeror\u00E1ln\u00ED kontraceptiva\nSou\u010Dasn\u00E9 u\u017E\u00EDv\u00E1n\u00ED atorvastatinu a peror\u00E1ln\u00EDch kontraceptiv vede ke zv\u00FD\u0161en\u00ED koncentrace norethisteronu a ethinylestradiolu. Toto zv\u00FD\u0161en\u00ED koncentrace mus\u00ED b\u00FDt zohledn\u011Bno p\u0159i d\u00E1vkov\u00E1n\u00ED peror\u00E1ln\u00EDch kontraceptiv.\nKolestipol\nPlazmatick\u00E1 koncentrace atorvastatinu a jeho aktivn\u00EDch metabolit\u016F byla sn\u00ED\u017Eena p\u0159i sou\u010Dasn\u00E9m u\u017E\u00EDv\u00E1n\u00ED atorvastatinu a kolestipolu (asi 25%), p\u0159i\u010Dem\u017E hypolipidemick\u00FD \u00FA\u010Dinek byl vy\u0161\u0161\u00ED ne\u017E u ka\u017Ed\u00E9ho p\u0159\u00EDpravku samostatn\u011B.\nAntacida\nP\u0159i sou\u010Dasn\u00E9m u\u017E\u00EDv\u00E1n\u00ED antacid obsahuj\u00EDc\u00EDch hydroxid hlinit\u00FD a ho\u0159e\u010Dnat\u00FD s atorvastatinem doch\u00E1z\u00ED ke sn\u00ED\u017Een\u00ED plazmatick\u00E9 koncentrace atorvastatinu a jeho aktivn\u00EDch metabolit\u016F o cca 35%. Sni\u017Eov\u00E1n\u00ED LDL-cholesterolu z\u016Fstalo v\u0161ak nezm\u011Bn\u011Bno.\nWarfarin\nSou\u010Dasn\u00E9 u\u017E\u00EDv\u00E1n\u00ED atorvastatinu a warfarinu vedlo b\u011Bhem prvn\u00EDch dn\u016F l\u00E9\u010Dby k m\u00EDrn\u00E9mu zkr\u00E1cen\u00ED protrombinov\u00E9ho \u010Dasu, prodlou\u017Een\u00E9ho p\u0159i terapii warfarinem. Stav se normalizuje v pr\u016Fb\u011Bhu 15 dn\u016F l\u00E9\u010Dby atorvastatinem. P\u0159esto je v\u0161ak t\u0159eba pacienty u\u017E\u00EDvaj\u00EDc\u00ED warfarin pe\u010Dliv\u011B kontrolovat, je-li k jejich l\u00E9\u010Db\u011B p\u0159id\u00E1n atorvastatin.\nFenazon\nSou\u010Dasn\u00E9 pod\u00E1v\u00E1n\u00ED opakovan\u00FDch d\u00E1vek fenazonu a atorvastatinu m\u00E1 mal\u00FD nebo \u017E\u00E1dn\u00FD \u00FA\u010Dinek na vylu\u010Dov\u00E1n\u00ED fenazonu.\nCimetidin\nV interak\u010Dn\u00ED studii s cimetidinem a atorvastatinem nebyly pozorov\u00E1ny \u017E\u00E1dn\u00E9 interakce.\nAmlodipin\nV interak\u010Dn\u00ED studii se zdrav\u00FDmi dobrovoln\u00EDky vedlo sou\u010Dasn\u00E9 u\u017E\u00EDv\u00E1n\u00ED atorvastatinu 80 mg a amlodipinu 10 mg k 18% zv\u00FD\u0161en\u00ED expozice atorvastatinu.\nDal\u0161\u00ED interakce\nKlinick\u00E9 studie neprok\u00E1zaly vz\u00E1jemn\u00E9 ovlivn\u011Bn\u00ED mezi atorvastatinem a antihypertenzivy nebo antidiabetiky.\n"@cs . . . . . . . . . . . "004.005" . . . . "Interakce s\u00A0jin\u00FDmi l\u00E9\u010Div\u00FDmi p\u0159\u00EDpravky a jin\u00E9 formy interakce"@cs . . .