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////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
////////////////////////////////////////////////////////////////////////////
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PŘÍLOHA ISOUHRN ÚDAJŮ O PŘÍPRAVKU1.NÁZEV VETERINÁRNÍHO LÉČIVÉHO PŘÍPRAVKUForthyron flavoured 400 μg tablety pro psy2.KVALITATIVNÍ A KVANTITATIVNÍ SLOŽENÍJedna tableta obsahuje: Léčivá látka:Levothyroxinum natricum hydricum 400 μg (odpovídá 389 μg levothyroxinum)Úplný seznam pomocných látek viz bod 6.1.3.LÉKOVÁ FORMATableta.Našedlá kulatá tableta s hnědými skvrnami rozdělená na čtyři části dělící rýhou. Tablety lze dělit na poloviny nebo čtvrtiny.4.KLINICKÉ ÚDAJE4.1Cílové druhy zvířatPsi.4.2Indikace s upřesněním pro cílový druh zvířatLéčba hypotyreózy u psů.4.3KontraindikaceNepoužívat u psů s nekorigovanou adrenální insuficiencí. Nepoužívat v případě známé přecitlivělosti na levothyroxin sodný nebo na některou z pomocných látek.4.4Zvláštní upozornění pro každý cílový druhDiagnóza hypotyreózy by měla být potvrzena vhodnými vyšetřeními. 4.5Zvláštní opatření pro použitíZvláštní opatření pro použití u zvířatTablety jsou ochucené. Aby se zabránilo náhodnému požití, uchovávejte tablety mimo dosah zvířat.Náhlé zvýšení poptávky po přívodu kyslíku do periferních tkání a chronotropní účinky levothyroxinu sodného mohou vystavit špatně pracující srdce nadměrné námaze, což způsobí dekompenzaci a příznaky kongestivního srdečního selhání. Psi s nedostatečnou funkcí štítné žlázy, trpící hypoadrenokorticismem, mají sníženou schopnost metabolizovat levothyroxin sodný, a proto jsou vystaveni zvýšenému riziku tyreotoxikózy. Psi se současným hypoadrenokorticismem a hypotyreózou by se měli stabilizovat léčbou glukokortikoidy a mineralokortikoidy před léčbou levothyroxinem sodným, aby se zabránilo vyvolání hypoadrenokortikální krize. Poté by se měly testy štítné žlázy opakovat s následným postupným zaváděním terapie levothyroxinem, začínající na 25 % normální dávky a rostoucí o 25 % každých čtrnáct dnů, dokud není dosaženo optimální stabilizace. Postupné zavádění terapie se rovněž doporučuje u psů s jinými souběžnými nemocemi, zejména diabetem mellitus a ledvinovou či jaterní dysfunkcí.Zvláštní opatření určené osobám, které podávají veterinární léčivý přípravek zvířatůmJakoukoliv nevyužitou část(i) tablety vraťte do otevřeného blistru pro použití při příštím podání.Po podání tablet si umyjte ruce. Těhotné ženy by měly s přípravkem zacházet obezřetně. V případě náhodného požití vyhledejte ihned lékařskou pomoc a ukažte příbalovou informaci nebo etiketu praktickému lékaři. Pro lékaře: Přípravek obsahuje vysokou koncentraci L-tyroxinu sodného a v případě požití může pro člověka, zejména děti, představovat riziko.4.6Nežádoucí účinky (frekvence a závažnost)Obnovení fyzické aktivity může odhalit nebo zvýraznit další obtíže související se zdravím, například osteoartrózu. Nežádoucí účinky hormonů štítné žlázy jsou všeobecně spojovány s nadměrným dávkováním a odpovídají příznakům hyperthyroidismu, včetně ztráty hmotnosti bez ztráty chuti k jídlu, hyperaktivity, vzrušivosti, lapání po dechu, tachykardie, polydipsie, polyurie a polyfágie. Velmi vzácně byly hlášeny hypersenzitivní účinky (pruritus). Viz také bod 4.10. Četnost nežádoucích účinků je charakterizována podle následujících pravidel:- velmi časté (nežádoucí účinek(nky) se projevil(y) u více než 1 z 10 ošetřených zvířat)- časté (u více než 1, ale méně než 10 ze 100 ošetřených zvířat)- neobvyklé (u více než 1, ale méně než 10 z 1000 ošetřených zvířat)- vzácné (u více než 1, ale méně než 10 z 10000 ošetřených zvířat)- velmi vzácné (u méně než 1 z 10000 ošetřených zvířat, včetně ojedinělých hlášení).4.7Použití v průběhu březosti, laktace nebo snáškyBezpečnost veterinárního léčivého přípravku nebyla stanovena pro použití u březích a kojících fen. Levothyroxin je však endogenní látkou a hormony štítné žlázy jsou zásadní pro vývoj plodu, zejména během prvního období gestace. Hypotyreóza během březosti může vést k závažným komplikacím, například narušenému vývoji plodů a fetální odúmrti. Léčené březí feny by se proto měly od zabřeznutí až do několika týdnů po porodu pravidelně monitorovat, protože požadavky na dávkování se mohou během březosti a laktace měnit. 4.8Interakce s dalšími léčivými přípravky a další formy interakceRůzná léčiva mohou narušovat vázání hormonů štítné žlázy v plazmě či v tkáni, případně pozměnit metabolismus hormonu štítné žlázy (např. barbituráty, antacidy, anabolické steroidy, diazepam, furosemid, mitotan, fenylbutazon, fenytoin, propranolol, velké dávky salicylátů a sulfonamidů). Při léčbě psů, kterým je podána souběžná medikace, by se vlastnosti těchto léčiv měly vzít v úvahu. Zvýšení dávky digitalis může být nezbytné u pacienta, který měl předchozí kompenzované kongestivní srdeční selhání a který je převeden na náhradní terapii hormony štítné žlázy. Estrogeny mohou zvýšit potřebu hormonu štítné žlázy.Ketamin může způsobit tachykardii a hypertenzi při použití u pacientů užívajících hormony štítné žlázy. Levothyroxin zvyšuje účinek katecholaminů a sympatomimetik. Při léčbě hypotyreózy u psů současně trpících diabetem se doporučuje pečlivé sledování stavu diabeta mellitu. Většina psů s dlouhodobou denní léčbou glukokortikoidy ve vysokých dávkách bude mít velmi nízké nebo nedetekovatelné sérové koncentrace T4, stejně jako subnormální hodnoty T3.4.9Podávané množství a způsob podáníPerorální podání.Doporučená výchozí dávka levothyroxinu sodného je 10 μg/kg živé hmotnosti perorálně každých 12 hodin. Kvůli variabilitě absorpce a metabolismu může být nutné změnit dávku předtím, než bude pozorována úplná klinická odezva. Počáteční dávka a frekvence podání jsou pouze výchozím bodem. Terapie musí být vysoce individuální a uzpůsobena požadavkům každého psa. Psům o nižší živé hmotnosti než 5 kg by měla být, na začátku dávkování, podána čtvrtina jedné 200 g tablety jednou denně. Takové případy je nutné pečlivě sledovat. Přítomnost potravy může ovlivnit u psů absorpci levothyroxinu sodného. Načasování léčby a její spojitost s krmením by se proto měla důsledně každý den dodržovat. Pro adekvátní sledování terapie by měly být změřeny spodní hodnoty (těsně před léčbou) a nejvyšší hodnoty (asi tři hodiny po podání) T4 v plasmě. U psů dostávajících adekvátní dávku by se nejvyšší plazmatické koncentrace T4 měly nacházet v oblasti vyšších hodnot normálního rozsahu hodnot (přibližně 30 až 47 nmol/l) a nejnižší hodnoty by se měly pohybovat přibližně okolo 19 nmol/l. Pokud jsou hladiny T4 mimo toto rozmezí, lze dávku levotyroxinu upravit v krocích po 50 až 200 µg pomocí vhodné síly (sil) tablet, dokud pacient není klinicky eutyroidní a T4 v séru není v referenčním rozmezí. Koncentrace T4 v plazmě lze opětovně stanovit za dva týdny po změně dávky, ale klinické zlepšení je stejně tak důležitým faktorem při stanovení individuální dávky, a to nastane za čtyři až osm týdnů. Jakmile bude dosaženo optimální substituční dávky, klinické a biochemické sledování lze provádět každých 6 až 12 měsíců.iVBORw0KGgoAAAANSUhEUgAAAksAAAJgCAIAAAAVtLCgAAAABGdBTUEAALGIlZj0pgAAAAlwSFlz
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Pro přesné a snadné rozlomení tablety položte tabletu dělící rýhou nahoru a zatlačte na ní palcem.Pro rozlomení tablety na dvě části; přidržte jednu polovinu tablety a stiskem směrem dolů odlomte druhou polovinu.4.10Předávkování (symptomy, první pomoc, antidota), pokud je to nutnéTyreotoxikóza by mohla nastat po podání nadměrných dávek. Tyreotoxikóza jakožto nežádoucí účinek mírného nadměrného podání je u psů vzácná díky jejich schopnosti katabolizovat a vylučovat hormony štítné žlázy. V případě náhodného podání velkého množství tablet Forthyronu lze snížit absorpci vyvoláním zvracení a jednorázovým společným podáním aktivního uhlí a síranu hořečnatého. Předávkování v podobě troj až šestinásobku doporučené počáteční dávky během čtyř po sobě jdoucích týdnů u zdravých, eutyroidních psů vedlo k nesignifikantním klinickým příznakům, které by bylo možno považovat za důsledek léčby. Jednorázové předávkování 3 až 6 násobkem doporučené dávky nepředstavuje pro psa riziko a nejsou nutná žádná opatření. Nicméně po dlouhodobém nadměrném podávání může teoreticky dojít ke vzniku klinických příznaků hypertyreózy, jako jsou polydipsie, polyurie, zrychlený dech, ztráta hmotnosti bez anorexie a společně či jednotlivě tachykardie a nervozita. Přítomnost těchto příznaků by měla vést k vyhodnocení koncentrací T4 v séru, aby se potvrdila diagnóza a okamžitě přerušilo podávání léčiva. Jakmile příznaky odezní (dny či týdny), dávka léčivého přípravku se přezkoumá a až se zvíře zcela zotaví, je možné začít podávat nižší dávky za pečlivého sledování zvířete. 4.11Ochranná(é) lhůta(y)Není určeno pro potravinová zvířata.5. FARMAKOLOGICKÉ VLASTNOSTI Farmakoterapeutická skupina: hormony štítné žlázy.ATCvet kód: QH03AA01.5.1Farmakodynamické vlastnostiFarmakologicky je levothyroxin klasifikován jako hormonální přípravek, který nahrazuje deficientní endogenní hormony. Thyroxin T4 je přeměňován na trijodthyronin T3. T3 působí na buněčné procesy prostřednictvím specifických interakcí ligand-receptor s jádrem, mitochondriemi a plazmatickou membránou. Interakce T3 s vazebnými místy vede k zesílené transkripci DNA nebo modulaci RNA, čímž se ovlivňuje proteosyntéza a enzymatická aktivita.Hormony štítné žlázy se podílí na mnoha odlišných buněčných procesech. Jsou nezbytné pro normální růst a vývoj, zejména centrálního nervového systému. Dodatečný přísun thyroxinu zvyšuje bazální buněčný metabolismus a spotřebu kyslíku, čímž v zásadě ovlivňuje funkci všech orgánových systémů. 5.2Farmakokinetické údajeU některých psů se ukazuje, že konzistentně buď lépe absorbují L-thyroxin a/nebo jej pomaleji odbourávají, než tomu je u jiných psů. Navíc je rychlost absorpce a odbourávání ovlivněna denním příjmem levothyroxinu sodného (vysoká absorpce/nízká eliminace v případě nízkého příjmu a naopak v případě vysokého příjmu). Proměnlivost farmakokinetických parametrů je mezi jednotlivými psy značná, a přestože přítomnost potravy může nepříznivě ovlivňovat absorpci, má se za to, že má malý účinek na celkové parametry. Absorpce je relativně pomalá a neúplná: Ve většině případů Tmax nastává od 1 do 5 hodin po perorálním podání, průměrná Cmax se mezi psy při stejných dávkách mění více než trojnásobně. U přiměřeně dávkovaných psů se vrchol píku v plasmě blíží nebo lehce překračuje horní hranici normálních koncentrací T4 v plazmě a do 12 hodin po perorálním podání obvykle klesá T4 v plazmě do spodní poloviny normálního rozpětí. Při hypotyreóze je vymizení T4 z plazmy zpomalené. Hlavním místem látkové přeměny tyroxinu (T4) jsou játra. L-tyroxin se váže na plazmatické bílkoviny a plazmatické lipoproteiny. Část dávky tyroxinu se metabolizuje dejodizací na biologicky aktivnější trijodthyronin (T3). Proces dejodizace pokračuje. Tyto další dejodizované metabolické produkty (jiné než T3 a T4) nemají tyreomimetický účinek. Jiné cesty metabolismu hormonu štítné žlázy zahrnují konjugaci za tvorby rozpustných glukuronidů a sulfátů pro biliární nebo urinární vylučování, jako i štěpení éterové vazby molekuly jodthyroninu. U psů je více než 50 % T4, produkovaného každý den, vyloučeno ve výkalech. Zásoby T4 mimo štítnou žlázu jsou odbourány a nahrazeny přibližně za 1 den. 6.FARMACEUTICKÉ ÚDAJE6.1Seznam pomocných látekDihydrát hydrogenfosforečnanu vápenatéhoMikrokrystalická celulosaSodná sůl karboxymethylškrobu (typ A)Magnesium-stearátPřírodní masové aroma6.2Hlavní inkompatibilityNeuplatňuje se.6.3Doba použitelnostiDoba použitelnosti veterinárního léčivého přípravku v neporušeném obalu: 2 roky.Doba použitelnosti zbylých částí tablety: 4 dny.6.4Zvláštní opatření pro uchováváníUchovávejte při teplotě do 25 C.Zbylé nepoužité části tablety vraťte zpět do blistru a spotřebujte do 4 dnů.6.5Druh a složení vnitřního obaluPřípravek je balen do blistrů (hliníková fólie (20 µm) – bílá fólie PVC/PE/PVDC (250/30/90)). 10 tablet v blistru, 5 nebo 25 blistrů v krabičce, 50 nebo 250 tablet v krabičce.Na trhu nemusí být všechny velikosti balení.6.6Zvláštní opatření pro zneškodňování nepoužitého veterinárního léčivého přípravku nebo odpadu, který pochází z tohoto přípravkuVšechen nepoužitý veterinární léčivý přípravek nebo odpad, který pochází z tohoto přípravku, musí být likvidován podle místních právních předpisů.7.DRŽITEL ROZHODNUTÍ O REGISTRACIEurovet Animal Health BVHandelsweg 25 5531 AE BladelNizozemsko8.REGISTRAČNÍ ČÍSLO (A)96/010/12-C9.DATUM REGITRACE/ PRODLOUŽENÍ REGISTRACEDatum registrace: 23. 1. 2012 Datum posledního prodloužení: 18. 12. 201710. DATUM REVIZE TEXTULeden 2021DALŠÍ INFORMACEVeterinární léčivý přípravek je vydáván pouze na předpis. PAGE \* MERGEFORMAT 6 PAGE \* MERGEFORMAT 1