Mokhoa oa ho sebelisa Zilt ea lithethefatsi?

Ka ho thibela ho tlama ha ADP ho li-receptor tse holim 'a liplatelete le ts'ebetso ea mochini oa GP IIb / IIIa, Clopidogrel inhibits e kopanetsoeng ke karolo ea methapo ea ADP. Clopidogrel e boetse e thibela ho kopana ha liplatelete ho bakoang ke lintho tse ling. Matla a Clopidogrel a phehella ho pholletsa le bophelo bohle ba liplatelete.
Ka tšebeliso ea nako e telele ea clopidogrel ka lethalleng la kalafo (75 mg / ka letsatsi), thibelo e tšoailoeng ea pokello ea liplatelete e se e le teng ka letsatsi la 1 la kalafo, ebe phello ea antiplatelet butle-butle e eketseha le ho fihla hofeta kamora matsatsi a 3-7 a tšebeliso ea kamehla ea lithethefatsi. Ka tšebeliso ea nako e telele ea clopidogrel ka lethal dose ea kalafo, thibelo e tloaelehileng ea "platelet aggregation" ke 40-60%. Kamora ho khaotsa kalafo, phello ea clopidogrel ho kopane le nako ea ho tsoa mali e nyamela, hangata kamora matsatsi a 5.
Kamora ho tsamaisoa ka molomo, clopidogrel e kenella ka potlako (nako ea ho fihlela mahloriso a mangata a plasma ke lihora tse 0,7-0.8). Kamora lihora tse peli, sethethefatsi ha se sa hlola se fumanoa plasma ea mali. Ho fufuleloa hoo e ka bang 50% mme ho ikemetse ka nko ea lijo. Karolo e ka sehloohong ea Clopidogrel le metabolite ea eona e ka sehloohong (ka ho latellana 98 le 94%) li khutlela morao ho liprotheine tsa plasma.
Clopidogrel ke setlhare. E tšelitsoe ka har'a sebete, metabolite ea mantlha e hlahisoang ke k'hemik'hale ea carboxylic acid. Khatello ea eona serapeng sa mali ke 85% ea kakaretso ea lithethefatsi. Ts'oarello e phahameng ka ho fetisisa serum ea mali e fihlella hoo e ka bang hora e le 'ngoe ka mor'a tsamaiso. Metabolite e sebetsang - the thiol derivative - e thehoa ke oxidation ea clopidogrel ho 2 - oxoclopidogrel, e lateloe ke hydrolysis. Oxidation ena e etsahala ka ho nka karolo ha cytochrome P450. Metabolite ena e sebetsang e ka khethollang in vitro, ka potlako le ka mokhoa o sa fetoheng e tlamahane le li-receptor tsa liplatelete mme e sitisa bongata ba tsona. Ha e fumanoe serum ea mali.
Kamora taolo e le 'ngoe kapa e pheta-phetoang ka moroto, 50% e hloekisoa,' me ka makhopho - 46% ea lethal dose e laoloang ea Clopidogrel. Bophelo ba halofo ea metabolite ea mantlha ka mor'a ts'ebetso e le 'ngoe kapa e pheta-phetoang ea lithethefatsi ke lihora tse 8.

Matšoao a ts'ebeliso ea lithethefatsi Zilt

Thibelo ea liketsahalo tse amanang le pelo le lefu la pelo (ischemic stroke, infraction ea myocardial le lefu la pelo) ho bakuli ba nang le lipontšo tsa kliniki ea atherosclerosis: ka lefu la ischemic (ho tloha matsatsing a 7 ho isa ho a 6), infraction ea myocardial (ho tloha matsatsing a 'maloa ho isa ho matsatsi a 35 kamora ho hlaseloa ke lefu la pelo), boteng ba mafu a methapo ea methapo ea kutlo.

Ts'ebeliso ea lithethefatsi Zilt

Tekanyetso e tloaelehileng ea bakuli ba baholo (ho kenyeletsa le ba tsofetseng) ke Letlapa le le leng (75 mg) ka letsatsi. Moriana o ka sebelisoa ho sa tsotelehe takatso ea lijo.
Nako ea kalafo ha e so theoe, empa li-regimens tsa kalafo ho fihlela likhoeli tse 12 li sebelisoa, phello e phahameng e lemohuoa kamora likhoeli tse 3 tsa ho nka moriana.

Mokhoa oa ts'ebeliso ea Zilt ka foromo ea letlapa

Ka hare, ho sa tsotelehe lijo tse jang, hang ka letsatsi.

Batho ba baholo le bakuli ba tsofetseng ba nang le ts'ebetso e tloaelehileng ea CYP2C19 isoenzyme

Myocardial infarction, ischemic stroke, kapa lefu le fumanehang la pherekano ea methapo ea methapo.

Zilt® e nooa ka tekanyetso ea 75 mg (pilisi e le 1) hang ka letsatsi.

Acute coronary syndrome ntle le karolo ea ST likarolo (engina e sa tsitsang kapa infarction ea myocardial ntle le leqhubu la Q)

Phekolo ka Zilt® e lokela ho qala ka tekanyo e le 'ngoe ea lethal dose ea ho laolla (300 mg), ebe e tsoela pele ka lethal dose ea 75 mg hang ka letsatsi (hammoho le acetylsalicylic acid ho litekanyetso tsa 75-325 mg ka letsatsi). Kaha tšebeliso ea litekanyetso tse phahameng tsa acetylsalicylic acid e amahanngoa le kotsi e kholo ea ho tsoa mali, lethal dose le khothalletsoang la acetylsalicylic acid ha lea lokela ho feta 100 mg. Phello e ntle haholo ea melemo e bonoa ke khoeli ea 3 ea kalafo. Nako e nepahetseng ea kalafo ea letšoao lena ha e khethoe ka semmuso. Liphetho tsa lithuto tsa tliliniki li netefatsa monyetla oa ho nka Clopidogrel ho isa ho likhoeli tse 12 kamora tsoelo-pele ea lefu la ho hlobaela ka popelong ntle le ho phahamisa karolo ea ST.

Acute coronary syndrome e nang le ST segment election (acute myocardial infarction) ka kalafo ea lithethefatsi le monyetla oa phekolo ea thrombolytic, hammoho le acetylsalicylic acid.

Zilt ® e lokela ho nooa ka tekanyetso ea 75 mg (pilisi e le 1) hang ka letsatsi, ho qala ka lethal dose ea ho loading, hammoho le acetylsalicylic acid le kapa ntle le thrombolytics. Bakeng sa bakuli ba lilemo tse ka tlase ho 75, kalafo e nang le Zilt® e lokela ho etsoa ntle le tšebeliso ea lethal dose. Phekolo ea ho kopanya e qaloa kapele ka mor'a ho qala ha matšoao mme e tsoela pele bonyane libeke tse 4. Ho sebetsa hantle ha kalafo e kopaneng le clopidogrel le acetylsalicylic acid e tšoarellang ho feta libeke tse 4 ha ho so ithutoe ho bakuli ba joalo.

Fibrillation ea Atrial (fibrillation ea atria)

Zilt® ea lithethefatsi e laetsoe ka tekanyetso ea 75 mg hang ka letsatsi. Hammoho le clopidogrel, kalafo e lokela ho qalisoa ebe ho kenella ha acetylsalicylic acid ka lethal dose ea 75-100 mg ka letsatsi e lokela ho tsoela pele.

Haeba mokuli a hlotsoe tekanyetso e latelang:

- haeba ho se ho fetile lihora tse 12 ka mor'a ho tlola tekanyetso e latelang, o lokela ho nka tekanyetso e lahlehileng ea Zilt® hang-hang, 'me u noe tekanyetso e latelang ka nako e tloaelehileng.

- haeba ho se ho fetile lihora tse 12 kamora ho tlola tekanyetso e latelang, lethal dose e latelang e lokela ho nooa ka nako e tloaelehileng, ha tekanyetso e sa lokela ho imena habeli.

Batho ba baholo le bakuli ba tsofetseng ba nang le ts'ebeliso ea liphatsa tsa lefutso ba fokotsehile ka CYP2C19 isoenzyme

Ketsahalo e tlase ea CYP2C19 isoenzyme e amahanngoa le ho fokotseha hoa phello ea antiplatelet ea clopidogrel. Ts'ebeliso ea Zilt® ho litekanyetso tse phahameng (lethal dose ea 600 mg, joale 150 mg hang ka letsatsi) ho bakuli ba nang le ts'ebetso e tlase ea CYP2C19 isoenzyme e lebisa ho eketseha ha phello ea antiplatelet ea clopidogrel (bona karolo ea Pharmacokinetics). Leha ho le joalo, litekong tsa bongaka tsa ho ithuta liphetho tsa bongaka, litekanyetso tse nepahetseng tsa litekanyetso tsa Clopidogrel ho bakuli ba nang le metabolism e fokotsehileng ka lebaka la ts'ebetso e tlase ea liphatsa tsa lefutso ea CYP2C19 isoenzyme ha ea ka ea thehoa.

Lihlopheng tse khethehileng tsa bakuli

Bakuli ba baholo

Ho baithaopi ba tsofetseng (lilemo tse fetang 75), ha ba bapisoa le baithaopi ba banyane, liphapang tsa ho kopanngoa ha liplatele le nako ea ho tsoa mali ha lia ka tsa senoloa. Phetoho ea moriana ho bakuli ba tsofetseng ha e hlokehe.

Ts'ebetso ea mokokotlo e sa sebetseng

Kamora ho sebelisoa khafetsa ha Clopidogrel ka tekanyo ea 75 mg ka letsatsi ho bakuli ba nang le bothata ba ho ruruha ha renal (CC 5-15 ml / min), tekanyo ea thibelo ea karolo ea methapo ea methapo ea ADP e 25% e tlase ho feta ho baithaopi ba phetseng hantle. Leha ho le joalo, tekanyo ea ho lelefatsa nako ea ho tsoa mali e ne e ts'oana le ea baithaopi ba phetseng hantle ba neng ba amohela Clopidogrel ka tekanyetso ea 75 mg ka letsatsi. Mamello ea lithethefatsi e ne e lokile ho bakuli bohle. Ts'ebetso ea sebete e sa sebetseng

Kamora ho sebelisa Clopidogrel ka tekanyo ea 75 mg ka letsatsi bakeng sa matsatsi a 10 ho bakuli ba nang le ts'ebetso e matla ea sebete, boemo ba thibelo ea methapo ea methapo ea methapo le phallo ea mali nakong e tlang bo ne bo bapisoa le baithaopi ba phetseng hantle.

Ho ata ha li-alleles tsa CYP2C19 isoenzyme tse amanang le mofuta o bohareng kapa o fokotsehileng oa metabolism li fapana pakeng tsa baemeli ba merabe e fapaneng / ea merabe (bona karolwana ea Pharmacogenetics). Lintlha tse fumanehang tsa lingoliloeng tse fumanehang bakeng sa ho lekola bohlokoa ba tlhaiso-leseling ea CYP2C19 isoenzyme liphellong tsa bongaka bakeng sa bakuli ba morabe oa Mongoloid.

Ha ba bapisa thepa ea pharmacodynamic ea clopidogrel ho banna le basali, basali ba bonts'itse thibelo e nyane ea ADP e kenyellelitsoeng liplatelete, empa ho ne ho sena phapang keketseho ea nako ea mali. Ha ho bapisoa clopidogrel le acetylsalicylic acid ho bakuli ba kotsing ea ho ba le mathata a ischemic, khafetsa liphetho tsa kliniki, litla-morao tse ling le ho kheloha molemong oa litekanyetso tsa kliniki le tsa laboratori li ne li tšoana ho banna le basali.

Litla-morao tsa lithethefatsi Zilt

Liphetoho tse akaretsang: bohloko ba sefuba, mokhathala, asthenia.
Ho tsoa tsamaisong ea methapo: ho opeloa ke hlooho, ho tsekela, paresthesia, maqhubu a leoto, hypesthesia, neuralgia, ho felloa ke letsoalo.
Ho tsoa ho tsamaiso ea methapo ea pelo: edema ea morao-rao, khatello ea mali (khatello e phahameng ea mali), ho nyekeloa ke pelo, tachycardia.
Ho tsoa pampiring ea ka mpeng: bohloko ba ka mpeng, ho opeloa ke lets'ollo, lets'ollo, ho nyekeloa, ho sokela, ho hlatsa, bolutu, ho khathatsoa hoa tatso, ho tlotsa ka liso tsa ka mpeng, hemorrhagic gastritis, mali a tsoang ka mpeng.
Karolong ea sebete le pampiri ea biliary: ts'ebetso e eketsehileng ea hepatic transaminases, hyperbilirubinemia, hepatitis, sebete steatosis.
Ho tsoa tsamaisong ea mali: thrombocytopenia, anemia (aplastic kapa hypochromic), agranulocytosis, granulocytopenia, leukocytosis, leukopenia, neutropenia.
Ho tsoa tsamaisong ea mali ea mali: nosebleeds, madi a tsoang ka mpeng, hemarthrosis, ho tsoa mali ho tsoa mochineng oa ho ruruha, hemoptysis, hemorrhage ea mali, ho tsoa mali ho tsoa mali, leqeba ho tsoa leqeba la postoperative, hemorrhage ka leiung, hemothorax, hemorrhage ea pulmonary, allergic purpura.
Ho tsoa ts'ebetsong ea musculoskeletal: bohloko ba morao, ramatiki, arthrosis.
Ho tloha lehlakoreng la tsamaiso ea methapo e bohareng: khatello ea maikutlo
Ho tsoa ts'ebetsong ea phefumoloho: ho ruruha ka mokhoa o ka holimo oa phepelo ea methapo, ho hema hanyane, rhinitis, bronchitis, khohlela, pneumonia, sinusitis.
Letlalo: lekhopho, ho hlohlona, eczema, ulcers ea letlalo, dermatitis e ngata, erythematous rash, ramatiki ea maculopapular, urticaria.
Ho tsoa lithong tsa kutlo: cataract, conjunctivitis.
Ho tsoa ts'ebetsong ea genitourinary: ts'oaetso ea ts'ebetso ea moroto, cystitis, hypermenorrhea, linyeoe tsa hemolytic uremic syndrome le nephropathy ea membrous.
Litla-morao: maemo a arohaneng a karabelo ea hypersensitivity (angioedema, bronchospasm, anaphylaxis).

Litaelo tse khethehileng bakeng sa ts'ebeliso ea lithethefatsi Zilt

Bakeng sa bakuli ba nang le myocardial infarction, ha ho khothalletsoe ho qala kalafo ka clopidogrel matsatsing a seng makae a qalang ka mor'a ho otloa ke lefu la pelo. Clopidogrel e eketsa nako ea ho tsoa mali. Moriana o lokela ho sebelisoa ka hloko ho bakuli ba nang le menyetla e eketsehileng ea ho tsoa mali ka lebaka la khatello ea maikutlo, ho kenella ka tšebetso ea ho buuoa kapa maemo a mang a methapo, hammoho le ho bakuli ba nang le tšollo ea mali (ho tsoa mali ka mpeng, hemorrhage ea mahlo). Phekolo ea Clopidogrel e lokela ho khaotsa bonyane matsatsi a 7 pele ho ts'ebetso e reriloeng ea ho buoa (ho kenyeletsoa lits'ebetso tsa meno).
Bakuli ba lokela ho lemosoa hore nakong ea kalafo ka clopidogrel, menyetla ea ho tsoa mali e eketseha le hore ho tsoa mali ho ka nka nako e telele ho feta ho tloaelehileng, ebe ho emisa hanghang. Ha u khaola likhahla tse nyane (nakong ea ho kuta) kapa likotsi tse ling tsa lelapa, ha ho hlokahale mehato e khethehileng ea ho emisa ho tsoa mali. Bakeng sa ho fokotsa kapa ho tsoa likotsi tse kholo, ho hlokahala tumellano ea bongaka e potlakileng.
Ka lebaka la boiphihlelo bo sa lekaneng ba "clopidogrel" ho bakuli ba nang le ts'ebetso ea renal e sa sebetseng, tlhokomeliso e lokela ho ba teng ha u sebelisa lithethefatsi.
Ka tlolo e kholo ea ts'ebetso ea sebete, menyetla ea ho tsoa mali e eketseha, ka hona, ho bakuli bana, Clopidogrel e lokela ho sebelisoa ka hloko.
Tšireletseho le katleho ea Clopidogrel ho bana le bacha ba ka tlase ho lilemo tse 18 ha e e-so thehisoe, ka hona, setlhare ha se ngoletsoe bakuli ba sehlopha sena sa lilemo.
Ka lebaka la khaello ea ya data, Clopidogrel ha e khothalletsoe hore e sebelisoe nakong ea kemaro le ho lactation.
Lithethefatsi li ka ama boemo ba psychophysical, bo bonahatsoang ke ho fokolisa tlhokomelo, ho fokotseha ha maikutlo a psychomotor mme ho hloka tlhokomeliso ha ho khanna makoloi le ha o sebetsa ka mekhoa e ka bang kotsi.

Ts'ebelisano ea lithethefatsi Zilt

Ka lebaka la kotsi e eketsehileng ea ho tsoa mali, tšebeliso ea nako e tšoanang ea Clopidogrel le warfarin ha e khothalletsoe. Ka tšebeliso e tšoanang ea Clopidogrel e nang le heparin kapa li-supporter tse ling tsa thrombolytic, menyetla ea ho tsoa mali e ka eketseha, ka hona ts'ebeliso e kopaneng ea lithethefatsi tsena e hloka tlhokomeliso. Ts'ebeliso e tšoanang ea Clopidogrel le NSAIDs e eketsa kotsi ea ts'ebetso ea ulcerogenic le nts'etsopele ea mali a tsoang liso, ka hona ts'ebeliso ea clopidogrel le NSAIDs e hloka tlhokomeliso.
Ka tšebeliso e tšoanang ea Clopidogrel e nang le atenolol, nifedipine, digoxin, phenobarbital, cimetidine, estrogen kapa theophylline, ha ho na ts'ebelisano e kholo ea kliniki e ileng ea hlokomeloa. Ho na le bopaki ba polokeho ea tšebeliso ea nako e le 'ngoe ea clopidogrel e nang le phenytoin le tobutamide.
Li-antacid ha li ame ho ajoa ha clopidogrel.

Bongata ba lithethefatsi Zilt, matšoao le kalafo

Nyeoe e le 'ngoe ea overopose ea ka boomo ea Clopidogrel e hlalosoa ha mosali ea lilemo li 34 ea nang le sepheo sa ho ipolaea a nka 1050 mg (matlapa a 14) a Clopidogrel. Ha ho na matšoao a bosholu kapa mathata a teng, ha ho kalafo e khethehileng e entsoeng.
Kamora ho amohela baithaopi ba phetseng hantle, 600 mg ea clopidogrel ha e a ka ea hlahisa litla-morao (ntle le keketseho ea makhetlo a 1,7 nako ea ho tsoa mali).
Ha ho na litlhare tse tobileng. Litlamorao tsa clopidogrel li ka felisoa ka ho tšeloa mali.

Foromo ea boholo:

Letlapa le 1 le koahetsoeng le na:

mantlha: ntho e sebetsang: clopidogrel hydrosulfate 97.875 mg, e baloa joalo ka clopidogrel 75,000 mg, baamohelang: lactose, anhydrous 108.125 mg, microcrystalline cellulose 30.00 mg, pregelatinized starch 12.00 mg, macrogol 6000 8.00 mg, oli ea castor, hydrogenated 4,00 mg,

khetla: hypromellose 6av 5.60 mg, titanium dioxide (E171) 1.46 mg, talc 0.50 mg, dae oxide red (E 172) 0,04 mg, propylene glycol 0,40 mg.

Matlapa a potolohileng, a biconvex hanyane, a kopantsoeng le koae ea filimi ea pinki.

* Ponahalo ea sefapano: 'mele o mosoeu kapa o batlang o le tšoeu o nang le sheath ea pinki.

Khemisi:

Clopidogrel ke setlhare, e 'ngoe ea li-metabolites tse sebetsang tsa eona e leng inhibitor ea pokello ea liplatelete. Metabolite e sebetsang ea clopidogrel ka mokhoa o ikhethileng e thibella ho tlama
adenosine diphosphate (ADP) e nang le P2Y_I2 li-receptor tsa liplatelete le tšebetso ea morao-rao ea ADP e pakeng tsa glycoprotein GPIIb / IIIa, e lebisang ho sitisong ea pokello ea liplatelete.

Khatello ea pokello ea liplatele ha e fetohe ebile e tsoela pele nakong eohle ea bophelo ba lisele (hoo e ka bang matsatsi a 7-10), ka hona, tekanyo ea ho khutlisetsoa hoa ts'ebetso e tloaelehileng ea liplatelete e lekana le sekhahla sa nchafatso ea bona. Phatlalatso ea liplatelete e hlahisitsoeng ke agonists ntle le ADP le eona e thibetsoe ka lebaka la thibelo ea ts'ebetso ea liplatelete e atisitsoeng ke ADP.

Metabolite e sebetsang e thehiloe ke ketso ea CYP450 isoenzymes, tse ling li ka fapana ka polymorphism kapa li ka thibeloa ke lithethefatsi tse ling, ka hona, ha se bakuli bohle ba nang le thibelo e lekaneng ea platelet aggregation.

Phekolo ka clopidogrel ka tekanyo ea 75 mg ka letsatsi ho tloha ka letsatsi la pele la kalafo, ho na le khatello e kholo ea tlatsetso ea methapo ea methapo ea ADP, eo butle-butle e eketsehang ka matsatsi a 3-7 ebe e fihla maemong a sa khaotseng (holim 'a ho lekana). Sebakeng sa tekano, tekanyo ea ho thibeloa ha liplatelese ha u sebelisa clopidogrel ka tekanyo ea 75 mg ka letsatsi, ka karolelano, e ne e le 40% ho isa ho 60%. Kamora ho emisa Clopidogrel, pokello ea liplatelete le nako ea ho tsoa mali butle-butle li ile tsa khutlela mekhoeng ea tsona ea pele, ka karolelano, ho feta matsatsi a 5.
Clopidogrel e ka thibela nts'etsopele ea mathata a atherothrombotic ho bakuli ba nang le liso tsa methapo ea methapo ea sebaka leha e le sefe, haholo-holo tse nang le methapo ea methapo ea methapo ea methapo kapa methapo.

Nts'iets'ing:

Kamora taolo e le 'ngoe le e pheta-phetoang ea molomo ka tekanyetso ea 75 mg ka letsatsi
clopidogrel e kenella ka potlako. Karolelano ea likhakanyo tse phahameng (C_m_Ah) clopidogrel e sa fetoheng ho plasma ea mali (2.2-2.5 ng / ml kamora ho ts'oaroa ka tekanyetso e le 'ngoe ea 75 mg) e fihlella kamora metsotso e ka bang 45. Ho latela liphuputso tse entsoeng ka ho pepesetsoa ha methapo ea li-metabolite tsa clopidogrel, tekanyo ea ho koaloa e batla e le 50%.

Clopidogrel le metabolite ea eona e sa sebetseng e potoloha ka plasma e khutlela liprotheine tsa plasma ea motho tlasa maemo in vitro (98% le 94%, ka ho latellana). Tlamo ena ha e kopane le maemo a mangata a fapaneng.

Clopidogrel e kenngoe ka matla sebeteng. Maemong in vitro le ho vivo
clopidogrel e tšelisoa ka mekhoa e 'meli: ea pele e hokahanngoe le litheko mme e lebisa ho hydrolysis ka sebopeho sa metabolite e sa sebetseng - derivative of carboxylic acid (85% ea metabolites ea potoloho), mme e ngoe e ts'oaroa ke li-isoenzymes tse fapaneng tsa cytochrome P450. Mathomong
clopidogrel e fetoloa metabolite e bohareng - 2-oxo-clopidogrel. Kamora metabolism ea morao-rao ea 2-oxo-clopidogrel e lebisa ho thehoeng hoa metabolite e sebetsang ea Clopidogrel - thiol e tsoang ho clopidogrel. Ka vitro, tsela ena e kopantsoe le isoenzymes CYP3A4, CYP2C19, CYP1A2 le CYP2B6. Acth thiol metabolite ea clopidogrel e arotsoeng tlas'a maemo in vitro, ka potlako le ka mokhoa o sa fetoheng o sebetsana le li-receptor tsa platelet, li thibela bongata ba tsona.

Le_m_Ah metabolite e sebetsang ka plasma ea mali ka mor'a ho nka tekanyetso ea ho loading (300 mg) ea clopidogrel e phahame habeli ho C_m_Ah kamora matsatsi a 4 a ts'ebeliso ea clopidogrel ka lethal dose ea tlhokomelo (75 mg / letsatsi). Le_m_Ah ka plasma ea mali e fumanoa metsotso e ka bang 30-60 kamora ho sebelisa moriana.

Kamora ho kenella ha Clopidogrel ea 14 C, hoo e ka bang 50% ea radioactivity eohle e hlahisoa ke liphio le hoo e ka bang 46% ke mala ka hare ho lihora tse 120 kamora ho hlohlona. Kamora taolo e le 'ngoe ea molomo ea Clopidogrel ka lethal dose ea 75 mg, halofo ea bophelo (T_1/2) ke hoo e ka bang lihora tse 6. T_1/2 metabolite e ka sehloohong e sa sebetseng e tsamaeang ka har'a plasma ea mali ka mor'a tšebeliso e le 'ngoe le e phetoang ke lihora tse 8.

Isoenzyme CYP2C19 e nka karolo ho thehoeng ha metabolite ka bobeli le metabolite e bohareng - 2-oxo-clopidogrel. Phello ea pharmacokinetics le antiplatelet ea li-clopidogrel metabolite tse sebetsang, hammoho le liphetho tsa tlhahlobo ea pokello ea liplatelete tlas'a maemo a ex vivo, li fapana ho latela mofuta oa CYP2C19 isoenzyme.

Allele ea CYP2C19 * 1 isoenzyme gene e tsamaisana le metabolism e sebetsang ka botlalo, athe mefuta ea CYP2C19 * 2 le CYP2C19 * 3 isoenzyme ha e sebetse. Alleles ea CYP2C19 * 2 le CYP2C19 * 3 isoenzyme e ikarabella bakeng sa ho fokotseha ha metabolism ho baemeli ba bangata ba mabelo a Caucasoid (85%) le Mongoloid (99%). Liqoso tse ling tse amanang le ho haella kapa ho fokotseha ha metabolism ha li sa tloaeleha ebile li kenyelletsa, empa ha li felle ho, mefuta ea CYP2C19 * 4, * 5, * 6, * 7 le * 8 isoenzyme.

Bakuli ba nang le CYP2C19 isoenzyme e tlase ba lokela ho ba le likarolo tse peli tsa ts'ebetso tse boletsoeng ka holimo ka tahlehelo ea ts'ebetso. Ho latela lipatlisiso tse phatlalalitsoeng, khafetsa ea genotypes e nang le ts'ebetso e tlase ea CYP2C19 isoenzyme, e tsamaeang le ho fokotseha ha metabolism, e batla e le 2% ho baemeli ba peiso ea Caucasoid, 4% ho batho ba morabe oa Negroid le 14% ho batho ba morabe oa Mongoloid. Ho na le liteko tsa ho tseba mofuta oa CYP2C19 isoenzyme. Ho latela liphuputso le tlhahlobo ea meta, e neng e kenyelletsa batho ba nang le ts'ebetso e phahameng haholo, e phahameng, e mahareng le e tlase ea CYP2C19 isoenzyme, phapang e kholo ponts'ong ea metabolite e sebetsang le tekanyo e tloaelehileng ea thibelo ea liphatlalatso tsa liplatelete tsa ADP tse hlahisitsoeng ke baithaopi ba nang le ts'ebetso e phahameng haholo, e phahameng le e bohareng ea isoenzyme. CYP2C19 e ne e le sieo. Ho baithaopi ba nang le mesebetsi e fokolang ea isoenzyme ena, ho pepesetsoa ha metabolite e sebetsang ho fokotsehile ha ho bapisoa le baithaopi ba nang le ts'ebetso e phahameng ea isoenzyme CYP2C19.

Ha u sebelisa Clopidogrel ho litekanyetso tsa 600 mg, lethal dose ea ho loanela / litekanyetso tsa 150 mg (600 mg / 150 mg) ho bakuli ba nang le metabolism e tlase, tlhahiso ea metabolite e sebetsang e ne e phahame ho feta ka mofuta oa kalafo oa 300 mg / 75 mg. Ntle le moo, tekanyo ea thibelo ea liplatelese tse kopaneng li ne li tšoana le tsa lihlopha tsa bakuli ba nang le ts'ebetso e phahameng ea CYP2C19 isoenzyme e amohelang.
clopidogrel ho latela morero oa 300 mg / 75 mg. Leha ho le joalo, regimen ea litekanyetso tsa Clopidogrel sehlopheng sa bakuli ba nang le ts'ebetso e tlase ea CYP2C19 isoenzyme ha e so tsebisoe lithutong tse kenyelletsang tlhahlobo ea liphetho tsa bongaka. Liteko tsa kliniki tse entsoeng ho fihlela joale ha li na sampole e sa lekaneng ea ho bona phapang liphellong tsa kliniki ho bakuli ba nang le ts'ebetso e fokolang ea CYP2C19 isoenzyme.

Pharmacokinetics ea lihlopha tse khethehileng tsa bakuli

Pharmacokinetics ea metabolite e sebetsang ea clopidogrel ka lihlopha tse ikhethang tsa bakuli (bakuli ba tsofetseng, bana, bakuli ba nang le ts'ebetso ea renal le hepatic) ha e so ithutoe.

Bakuli ba baholo

Ts'ebetso ea mokokotlo e sa sebetseng

Kamora ho sebelisoa khafetsa ha Clopidogrel ka tekanyo ea 75 mg ka letsatsi ho bakuli ba nang le bothata ba ho ruruha ha renal (CC 5-15 ml / min), tekanyo ea thibelo ea karolo ea methapo ea methapo ea ADP e 25% e tlase ho feta ho baithaopi ba phetseng hantle. Leha ho le joalo, tekanyo ea ho lelefatsa nako ea ho tsoa mali e ne e tšoana le ea baithaopi ba phetseng hantle ba amohetseng
Clopidogrel ka tekanyo ea 75 mg ka letsatsi.

Ts'ebetso ea sebete e sa sebetseng

Contraindication

- Hypersensitivity ho clopidogrel kapa eng kapa eng e hlahisang lithethefatsi,

- ho hloka matla ha sebete,

- ho tsoa mali haholo, joalo ka ho tsoa mali ho tsoa ho peptic ulcer kapa hemorrhage ea intracranial,

- khaello ea lactase, ho se mamellane ha lactose, tsoekere ea glucose-galactose malabsorption,

- boimana le nako ea ho anyesa,

- Bana ba ka tlase ho lilemo tse 18 (polokeho le katleho ha e thehiloe).

Ka tlhokomelo:

- Sebete se sa sebetseng hantle sa ho sebetsa ha sebete se nang le monyetla oa ho tsoa mali (boiphihlelo bo fokolang)

- mosebetsi o sa sebetseng oa renal (boiphihlelo bo fokolang)

- maemo a phelisang a eketsang kotsi ea ho tsoa mali (ho kenyelletsa ho sithabela maikutlo, ho buuoa (bona karolo "Litaelo tse ikhethang"),

- mafu ao ho nang le 'ona a tlang pele ho ts'ebetso ea ho tsoa mali (haholo-holo ka mpeng)

- ts'ebeliso e le 'ngoe le lithethefatsi tse seng khahlanong le ts'oaetso tsa kokoana-hloko (NSAIDs), ho kenyelletsa le cycloo oxygenase-2 inhibitors (COX-2),

- tšebeliso e tšoanang ea warfarin, heparin kapa glycoprotein IIb / IIIa inhibitors

- bakuli ba nang le ts'ebetso e tlase ea CYP2C19 isoenzyme (ha ba sebelisa dopopidogrel ho litekanyetso tse khothalletsoang, metabolite e sa sebetseng ea Clopidogrel e thehiloe mme phello ea eona ea antiplatelet ha e bue haholo, ka hona, ha ho sebelisoa Clopidogrel ho litekanyetso tse khothalletsoang bakeng sa lefu la methapo ea methapo kapa ho kenella ka hare ho methapo ea methapo ea methapo, ho ka ba le sekhahla sa pelo. phahameng ho feta ho bakuli ba nang le ts'ebetso e tloaelehileng ea isoenzyme CYP2C19),

hypersensitivity ho li-thienopyridine tse ling (e.g.
ticlopidine, prasugrel) (bona karolo "Litaelo tse ikhethang").

Bokhachane le pelehi:

Kaha ha ho na datha ea kliniki mabapi le ts'ebeliso ea clopidogrel nakong ea kemolo, setlhare ha se khothalletsoe hore se sebelisoe nakong ea kemolo. Boithuto ba liphoofolo ha boa senola phello e mpe kapa e sa tobang ho ima, nts'etsopele ea "lehe le emolisitsoeng" - nakong ea ho pepa kapa ea pelehi.

Boithuto ba liphoofolo bo bontšitse seo
Clopidogrel le / kapa metabolites ea eona li epuoa lebeseng la matsoele. Ka hona, haeba ho hlokahala, kalafo
Clopidogrel om e khothalelitsoe ho emisa ho anyesa.

Tekanyetso le tsamaiso

Ka hare, ho sa tsotelehe lijo tse jang, hang ka letsatsi.

Batho ba baholo le bakuli ba tsofetseng ba nang le ts'ebetso e tloaelehileng ea CYP2C19 isoenzyme

Myocardial infarction, ischemic stroke, kapa lefu le fumanehang la pherekano ea methapo ea methapo.

Zilt® e nooa ka tekanyetso ea 75 mg (pilisi e le 1) hang ka letsatsi.

Acute coronary syndrome ntle le karolo ea ST likarolo (engina e sa tsitsang kapa infarction ea myocardial ntle le leqhubu la Q)

Acute coronary syndrome e nang le ST segment election (acute myocardial infarction) ka kalafo ea lithethefatsi le monyetla oa phekolo ea thrombolytic, hammoho le acetylsalicylic acid.

Fibrillation ea Atrial (fibrillation ea atria)

Haeba mokuli a hlotsoe tekanyetso e latelang:

- haeba ho se ho fetile lihora tse 12 ka mor'a ho tlola tekanyetso e latelang, o lokela ho nka tekanyetso e lahlehileng ea Zilt® hang-hang, 'me u noe tekanyetso e latelang ka nako e tloaelehileng.

- haeba ho se ho fetile lihora tse 12 kamora ho tlola tekanyetso e latelang, lethal dose e latelang e lokela ho nooa ka nako e tloaelehileng, ha tekanyetso e sa lokela ho imena habeli.

Batho ba baholo le bakuli ba tsofetseng ba nang le ts'ebeliso ea liphatsa tsa lefutso ba fokotsehile ka CYP2C19 isoenzyme

Lihlopheng tse khethehileng tsa bakuli

Bakuli ba baholo

Ts'ebetso ea mokokotlo e sa sebetseng

Kamora ho sebelisoa khafetsa ha Clopidogrel ka tekanyo ea 75 mg ka letsatsi ho bakuli ba nang le bothata ba ho ruruha ha renal (CC 5-15 ml / min), tekanyo ea thibelo ea karolo ea methapo ea methapo ea ADP e 25% e tlase ho feta ho baithaopi ba phetseng hantle. Leha ho le joalo, tekanyo ea ho lelefatsa nako ea ho tsoa mali e ne e tšoana le ea baithaopi ba phetseng hantle ba amohetseng
Clopidogrel ka tekanyo ea 75 mg ka letsatsi. Mamello ea lithethefatsi e ne e lokile ho bakuli bohle. Ts'ebetso ea sebete e sa sebetseng

Litla-morao

Tšireletseho ea clopidogrel e ntse e hlahlojoe ho bakuli ba fumaneng phekolo ea Clopidogrel selemo se le seng kapa ho feta. Tšireletseho ea Clopidogrel ka tekanyo ea 75 mg ka letsatsi e ne e ka bapisoa le ea acetylsalicylic acid ka lethal dose ea 325 mg ka letsatsi, ho sa tsotelehe lilemo, bong le morabe. Karabelo e mpe e bonoang litekong tsa bongaka e thathamisitsoe ka tlase. Ntle le moo, ho tlalehiloe litlaleho tsa boithatelo ba karabelo e mpe.

Lithutong tsa bongaka le ho shebella ha Clopidogrel ka mor'a ho rekisa, ho nts'etsopele ea ho tsoa mali ho ne ho tlalehiloe hangata, haholoholo khoeling ea pele ea kalafo.

Tlhalo ea liketsahalo tsa litlamorao tsa Mokhatlo oa Lefatše oa Bophelo (WHO): khafetsa? 1/10, hangata ho tloha ho 1/100 ho isa ho 1/10000 ho isa ho

Sokolla foromo le sebopeho

Foromo ea litekanyetso - matlapa a koahetsoeng ka filimi: pota, biconvex e 'mala o mopinki, pinki, motheo oa eona o na le sebopeho se soeufetseng kapa se soeufetseng (7 ka marang-rang, ka har'a lilakane tsa likarete tse 2, 4 kapa 12).

Ntho e sebetsang ke Clopidogrel hydrosulfate, letlapeng le le leng - 97.875 mg, kapa Clopidogrel - 75 mg.

Likarolo tse thusang: "cellcose" ea cellcrystalline, lactose e nang le enjine, starch ea pregelatinized, oli ea hydrogenated castor, macrogol 6000.

Sebopeho sa khetla ea filimi: propylene glycol, hypromellose 6cp, talc, titanium dioxide (E171), dae oxideide red (E172).

Moqapi le theko

K'hamphani ea litlama e kenyang tlhahiso ea moriana oa Zilt Russia KRKA. Hape, ka 'marakeng oa lehae, ka linako tse ling u ka fumana lithethefatsi tse tsoang kantle tse fanoeng ho tsoa Slovenia.

Ke "Zilt", ka bomalimabe e theko e phahameng haholo. Pele, theko ea sethethefatsi sena e itšetleha ka palo ea mabokose a kentsoeng ka lebokoseng. Mohlala, matlapa a 14 a sehlahisoa sena a jang chelete e ka bang 500-600 r, ho latela mofani. Bakeng sa marang-rang a 12, o tla tlameha ho lefa ho feta 2000 p. Leha ho le joalo, sethethefatsi sena se tšeloa meriana ea litlama feela ka taelo ea ngaka.

Ketso ea pharmacological

Sebakeng sa tšenyo ea methapo 'meleng oa motho, liplatelese li lula li qala ho bokellana. Ka nako e ts'oanang, li khomarelana 'me li khomarela lisele. Ts'ebetso ena e phethela ka ho etsoa ha seaparo sa mali.

Lithethefatsi "Zilt", litaelo tsa tšebeliso e bonolo haholo, li qala ho sebetsa hantle ho mokuli kapele haholo - metsotso e ka bang 30 ka mor'a taolo. Ha e kenella ka har'a 'mele oa motho, ho ba le tšitiso ea lintho tse tlatsetsang lipokothong. Ka tšebeliso ea kamehla ea lithethefatsi tsena ka mor'a matsatsi a ka bang 4-7, phello e matla ea kalafo e etsahala.

Khokahano e phahameng ea moriana ona 'meleng o hlaha lihora tse' maloa ka mor'a hore li tsamaisoe. Ho feta moo, litaba tsa eona maling le nakong ena hangata li tlase haholo.

Setlhare sena se nkoe 'meleng ho tsoa lipelong le lipelong. Nako ea halofo ea bophelo kamora tekanyetso e le 'ngoe e ka ba lihora tse 6-8.

Lithethefatsi "Zilt": litaelo tsa tšebeliso

Moriana ona oa fumaneha, joalo ka ha ho se ho boletsoe, o fumaneha feela ka mokhoa oa matlapa. Ka tumellano, ba e sebelisa feela ka molomo. Matlapa a nooa a 75 mg "Zilt" litaelo tsa ts'ebeliso li lumella ka bobeli pele ho lijo, le ka mor'a kapa nakong ea eona. Mekhoa ea ho sebelisa sethethefatsi sena e ipapisitse le lefu le itseng.

Mokuli ea nang le infraction ea myocardial hangata o beoa letlapa le le leng la 75 mg ka letsatsi. Litekanyetso tse tšoanang li fuoe bakuli ba nang le kotsi ea ischemic cerebrovascular and arterial occlusion. Tabeng ena, bakeng sa bakuli ba nang le myocardial infarction, moriana ona o ka laeloa nakong ea matsatsi a 1 ho isa ho a 35 a kholo ea lefu lena. Bakuli ba nang le lefu la "ischemic stroke" hangata ba laetsoe ho tloha matsatsing a 7 ho isa likhoeling tse tšeletseng.

Ka coronary syndrome e nang le sekhahla sa ST, moriana ona o boetse o beoa ka bongata ba 75 mg ka letsatsi. Empa ntlheng ena, pele ho nako mokuli o nka tekanyo e le 'ngoe ea ho laolla hammoho le aspirin le thrombolytics.

Ka coronary syndrome ntle le ST Elevation, ho sebelisoa mofuta o fapaneng o fapaneng oa kalafo. Maemong ana, hangata moriana o nooa ka tsela e latelang:

nwa moriana oa ho loading oa 300 mg hang

noara lithethefatsi letsatsi le leng le le leng ho 1 pilisi ka letsatsi.

Ntle le moo, hammoho le meriana le "aspirin" ka bongata ba 75-325 mg, lethal dose la letsatsi le leng le le leng la Zilt le lokela ho ba 100 mg. Ka regimen ena, phello e phahameng ho bakuli hangata e bonoa kamora likhoeli tse tharo. Mokhoa oa kalafo hangata hangata ke likhoeli tse 12.

Phekolo e joalo e laeloa maemong a mangata ho bakuli ba baholo ba ka tlase ho lilemo tse 75.

Litaelo tsa tšebeliso ea lithethefatsi "Zilt": contraindication

Bakeng sa bacha ba ka tlase ho lilemo tse 18, "Zilt" ha e fuoe thibelo ea lefu la tsoekere. Ha ho kgothaleloe ho nka moriana ona ho basali ba anyang le baimana. Clopidogrel e khona ho kenella, ho kenyelletsa, ho lebese la matsoele.

Ho joalo, u ke ke ua nka sethethefatsi sena le batho bao ba ka bang le karabelo ea mefuta eohle ea likarolo tsa eona. Na contraindication mabapi le ts'ebeliso ea "Zilt":

Ho latela litaelo tsa ts'ebeliso, "Zilt" e lokela ho nkuoa ka hloko ha ho hlaha mathata a kang:

hypersensitivity ho thienopyridines,

mesebetsi e tlase ea CYP2C19,

ho se sebetse hantle ha sebete le liphio,

maloetse ao ho tsoa mali ho ka etsahalang,

ts'ebetso ea opereishene le likotsi tse ka bakang mali.

Tšebelisano

Ntle le moo, ka hloko ho lokela ho nkuoa, ho latela litaelo tsa ts'ebeliso, "Zilt" 75 mg ka nako e le ngoe ka mekhoa e kang:

Ho etsahala se tšoanang kalafong e rarahaneng le lithethefatsi tse sa thibeleng tsa Zilt le tse senang mali.

Litlamorao tsa ho sebelisa meriana ena li ka fokotseha haeba mokuli a sebelisitse kalafo a sebelisa:

"Ticlopidine" le lithethefatsi tse ling.

Seo bakuli ba hlokang ho se tseba

Bakuli ba nkang Zilt ba tlameha ho latela litlhahiso tse latelang:

linyeoe tsa ho fumaneha ho sa tloaelehang kapa nako ea ho tsoa mali e lokela ho tlaleheloa ngakeng,

lingaka tsa meno le lingaka tse buoang li lokela ho tsebisoa ka nako ea kalafo le Zilt haeba li ka ikopanya.

Litlamorao li ka hlaha

Joalo ka moriana o mong o mong, Zilt e ka ba le litlamorao tse mpe 'meleng oa mokuli. Hangata, ha a fetisa thupelo a sebelisa moriana ona, litlamorao tse latelang li bonoa ho bakuli:

bohloko ba ka mpeng le lets'ollo,

Ka linako tse ling, ba noang ena lithethefatsi le bona ba ka iponahatsa:

ho hlohlona kapa ho hlohlona

hemorrhea ka mahlong,

Litekong tsa mali tsa laboratori, ho fokotseha ha lipalo tsa liplatelese le li-neutrophils ka linako tse ling ho ka bonoa ho bakuli.

Ho na le litla-morao tse ngata tsa meriana ena. Ka hona, litaelo tsa ts'ebeliso ea "Zilt" 75 mg li lokela ho tsotelloa ntle le tšenyo ea nako. Li-overd tsa moriana ona, ehlile, li ka se mamelloe. Haeba ka tšohanyetso mokuli a lebala ho nka pilisi ka letsatsi le leng, ho nooa tekanyetso habeli ka letsatsi le hlahlamang ha ho khothaletsoe boemong bofe kapa bofe.

Ho latela litaelo tsa tšebeliso, matlapa a Zilt, joalo ka a mang, ha a lokela ho tahoa haeba o khahlapetsoa ke eng kapa eng ea likarolo tsa ona. Boitšoaro bo joalo ha u sebelisa sethethefatsi sena ke seoelo. Empa ka nako e 'ngoe ho kulisa ho bakuli ba ntseng ba fuoa kalafo ba sebelisa pheko ena ho ntse ho ka bonoa. Boitšoaro bo atileng haholo ke:

hypersensitivity ho thienopyridine.

Seo u lokelang ho se etsa haeba ho na le overdose

Ho sebelisa lithethefatsi ka tlolo ea litaelo tsa ts'ebeliso ea "Zilt" ho lebisa ho hlaheng ha mathata a kang:

ho tsoa mali ka tlhaho e fapaneng,

ho eketsa nako ea ho tsoa mali.

Phekolo ea meriana e mengata haholo ka moriana ona ke matšoao. Hangata bakuli ba tšeloa mali ka bongata.

Menahano ea lithethefatsi

E bitsa "Zilt", joalo ka ha ho se ho boletsoe, e theko e boima. Ka hona, bakuli ba bangata, ba na le thahasello ea hore na ho na le lithethefatsi life tse theko e tlaase li ka nkang sethethefatsi sena haeba ho hlokahala.

Synonyms of drug "Zilt" ke, ka mohlala:

Lichelete tsena kaofela ka sebopeho sa tsona li na le ntho e le 'ngoe e sebetsang le Zilt. Haeba ho hlokahala, sethethefatsi sena se ka nkeloa sebaka ka nako efe kapa efe ka e 'ngoe ea liemeli tse lenaneng. Litaelo tsa ho sebelisoa le Zilt le lipapiso tsa eona li batla li ts'oana. Lithethefatsi tsena li fokotsa ho ruruha ha mali hantle. Leha ho le joalo, e ntse e lumelloa ho fetola Zilt ho efe kapa efe ea lipapatso tsena feela kamora ho buisana le ngaka pele.

Li-generator tsa Zilt ke meriana Clopidogrel (e theko ea 190 p. Bakeng sa li-pcs tse 14) le Clopidogrel Richter (292 p).

Likhatiso tsa moriana ona, le tsona tse thibelang ho fetoha ha mali, li ka tsela e latelang:

"Phenilin" e laeloa bakuli ho 0.025-0.1 g makhetlo a 1-3 ka letsatsi. Bakuli ba ka nka Dicumarin ho litekanyetso ho tloha 0,05 ho isa ho 0,1 g makhetlo a 2-3 ka letsatsi. Lingaka li beha Heparin ho bakuli ntle ho tšitiso, ka methapo kapa ka mokokotlong.

Hape, lithethefatsi "Plavix" li bua ka li-analogues tsa moriana ona. "Zilt", litaelo tsa tšebeliso eo re e hlahlobileng ka holimo, ha e le hantle, ke eona e nkang theko e tlase bakeng sa moriana ona. Bakuli ba bangata, ba fuoang chelete e lekaneng, ba eletsoa hore ba khethe Plavix bakeng sa thibelo ea thrombosis. Mabapi le ts'ebetso, Zilt e nyane hanyane ho moriana ona o bitsitsoeng.

Maemo a polokelo

Ehlile, ho nka thibelo ea mali a marang-rang e lokela ho ba lithethefatsi tse sa lefelloeng feela "Zilt". Ho khothalletsoa ho boloka moriana ona ka mocheso ho fihlela ho +25 ° C. Ka mantsoe a mang, lehlabuleng hoa hlokahala ho beha litafole tsena ka sehatsetsing. Bophelo ba lishelefing tsa sethethefatsi se pakiloeng se tiisitsoeng ke lilemo tse 3.

Litlhahlobo mabapi le pheko e tsoang ho bakuli

Bakuli ba na le maikutlo a matle ka meriana ena. Bakuli ba amana le melemo ea eona:

ho hloka litlamorao tse mpe ka mpeng.

Moriana ona o hlapolla mali, ho latela bakuli ba bangata, a le betere ho feta aspirin e tšoanang. Ka mantsoe a mang, kotsi ea ho hlaseloa ke pelo khafetsa kapa ho otloa ha e sebelisoa ka thata ho latela litaelo tsa ts'ebeliso, Zilt, litekolo tseo ho tsona ena e leng hantle feela, li fokotsang haholo.

Likotsi tse ling tsa meriana ena, bakuli ba nahana:

ha e bonolo haholo ho paka.

Ho hlaseloa ke pelo le stroke ho joalo, ho batho ba lilemo li mahareng. Empa hangata ho fapana le hoo, batho ba baholo ba ntse ba tobana le bothata bona. 'Me ehlile, ho reka sethethefatsi se joalo se theko e phahameng hangata ho thata.

Matlapa a Zilt a pakiloe ka marang-rang a nang le matsoho. Mohlomong moetsi ka hona o ne a batla ho etsa hore tšebeliso ea meriana ena ea letsatsi le letsatsi e be bonolo haholoanyane. Le ha ho le joalo, ho ea ka bakuli ba bangata, ho ka ba molemo haholo ho lokolla lipilisi tsena ka lithutsoana tse matla tseleng ea ho phatloha.

Phoso e 'ngoe ea moriana oa Zilt ke hore bakuli ba bangata ba e nka e na le phello e matla sebeteng. Boholo ba bakuli ba khothaletsa ho sebelisa meriana ena feela tlas'a taolo ea ngaka.

Lingaka li nahana eng ka moriana

Lingaka ka botsona li boetse li nka Zilt e le tsela e ntle ea ho fokotsa mali. Lisosa tsa moriana ona, lingaka li amahanya haholo le taba ea hore e mamella hantle bakuli ba bangata. Ho lekola litekolo, li-hemorrhage ka nako ea ts'ebeliso ea tsona li fumaneha seoelo.

Motheo oa bopaki mabapi le polokeho le katleho ea moriana ona, joalo ka lingaka tse ngata li hlokometse, o hantle haholo. Leha ho le joalo, ba lumela hore lithethefatsi li maemong afe kapa afe a tebileng. Lingaka lia intlafatsa hore li se ke tsa thuisa ka tšebeliso ea eona.

Litaelo tsa ho sebelisa Zilt: mokhoa le litekanyetso

Matlapa a nooa ka molomo, ho sa tsotelehe lijo.

Tekanyetso e khothalelitsoeng bakeng sa bakuli ba ts'ebetso e tloaelehileng ea CYP2C19 isoenzyme, ho kenyelletsa le bakuli ba tsofetseng:

Myocardial infarction, ischemic stroke kapa lefu le fumanoang le amanang le lefu la sethoathoa: 75 mg hang ka letsatsi,
Acute coronary syndrome ntle le karolo ea ST dikarolo (e sa tsitsang angina le myocardial infarction ntle le Q wave): lethal dose - hang ha 300 mg, ebe 75 mg hang ka letsatsi hammoho le acetylsalicylic acid ka lethal dose ea 75-325 mg ka letsatsi. Ha u fana ka taelo, ho lokela ho hopoloa hore litekanyetso tsa acetylsalicylic acid tse ka holimo ho 100 mg li amahanngoa le kotsi e kholo ea ho tsoa mali. Tšusumetso ea kalafo e etsahala khoeling ea 3 ea kalafo, bakeng sa liphetho tse ntle, ho bohlokoa hore u tsoele pele ho sebelisa Clopidogrel ho isa ho likhoeli tse 12,
Acute myocardial infarction (acute coronary syndrome e nang le sekhahla se phahameng sa ST): tekanyo e le 'ngoe ea ho laolla, ebe 75 mg hang ka letsatsi e kopane kapa e se na acetylsalicylic acid le thrombolytics. Ha ho kgothaletswe ho sebelisa litlolo tsa kalafo kalafo ea bakuli ba lilemo tse ka tlase ho 75. Phekolo e lokela ho qala ha matšoao a pele a lefu a hlaha mme a tsoela pele bonyane libeke tse 4,
Fibrillation ea Atrial (fibrillation ea atria): 75 mg hang ka letsatsi hammoho le asiti ea acetylsalicylic ka lethal dose ea 75-100 mg ka letsatsi.

Ho khothalletsoa ho nka matlapa ka nako e le 'ngoe, haeba u lieha ho feta lihora tse 12, o lokela ho nka tekanyetso e lahlehileng le e latelang ka nako e tloaelehileng, nako ea ho lekana pakeng tsa tekanyetso ea lihora tse fetang 12 - tekanyetso e latelang e nkuoa ntle le ho phetoa habeli.

Ho bakuli ba nang le ts'ebetso e fokotseng ea liphatsa tsa lefutso ea CYP2C19 isoenzyme ha ba nka Zilt ka litekanyetso tse khothalletsoang, sebopeho sa metabolite e sebetsang ea Clopidogrel se etsahala hanyane mme phello ea eona ea antiplatelet ha e phatlalatsoe. Tekanyetso e nepahetseng bakeng sa bakuli ba mokha ona ha e so theoe, hangata, moriana o laetsoe litekanyetso tse phahameng o na le tekanyetso e le 'ngoe ea lethal dose ea 600 mg mme ebe o ka bang le 150 mg hang ka letsatsi.

Bakuli ba tsofetseng ha ba hloke phetoho ea litekanyetso.

Litlamorao

Ho tsoa ho tsamaiso ea methapo ea pelo: hangata - hematoma, ka seoelo - arterial hypotension, vasculitis,
Ho tsoa ho hematopoietic system: infrequently - leukopenia, thrombocytopenia, eosinophilia, ka seoelo neutropenia, ho kenyelletsa le mefuta e matla, haholo ka seoelo, "aplasic anemia"
Ho tsoa ho tsamaiso ea tšilo ea lijo: hangata - bohloko ba ka mpeng, ho tsoa mali ka mpeng, lets'ollo, dyspepsia, hangata - ho nyekeloa, ho hlatsa, ho ruruha, gastritis, lefu la ho ruruha le leqeba la ka mpeng le, kapa ka seoelo - pancreatitis, ho khutlisetsa mali morao le mokokotlo (ho kenyelletsa le phello e bolaeang), colitis (ho kenyeletsa le lymphocytic), ho hloleha ka matla ha sebete, hepatitis, ho senyeha hoa tšebetsong ha sebete, stomatitis,
Ho tloha lehlakoreng la ts'ebetso ea methapo: hangata - hlooho e bohloko, hemorrhage e kenang (ho kenyeletsa le phello e bolaeang), kizunguzungu, paresthesia, ka seoelo - pherekano, hallucinations,
Ho tsoa ts'ebetsong ea musculoskeletal: ka seoelo - hemarthrosis, hemorrhage ea mesifa, ramatiki, myalgia, arthralgia,
Ho tloha tsamaisong ea phefumoloho: khafetsa - nosebleeds, ka seoelo - bronchospasm, ho tsoa mali ho tsoa phepelong ea phefumoloho (pulmonary hemorrhage, hemoptysis), interstitial pneumonitis,
Ho tsoa ts'ebetsong ea genitourinary: hangata - hematuria, ka seoelo - glomerulonephritis, keketseho ea serum creatinine,
Letlalong la letlalo: khafetsa - hematoma e subcutaneous, hangata - ho hlohlona ha letlalo, lekhopho, hemorrhages ea letlalo (hangata), haholo - - bulous dermatitis (Stevens-Johnson syndrome, chefo e matla ea methapo ea methapo ea methapo, erythema multiforme), uritisaria, rrythematous rash, lichen planus. eczema
Ho tsoa lithong tsa maikutlo: khafetsa - hemorrhage e khutlang kapa e kopaneng, ka seoelo - vertigo, ka seoelo - li-pathologies tsa tatso,
Matšoao a laboratori: khafetsa - ho fokotseha hoa lipalo tsa liplatelese le li-neutrophils, ho lelefatsa nako ea ho tsoa mali,
Litlamorao: Hoa tloaeleha - eczema, angioedema, anaphylactoid, lefu la serum, mokokotlo o sa tsejoeng - litheko tsa lithethefatsi tse nang le matšoao a lefu la DRESS le eosinophilia, hypersensitivity ea thienopyridines, hypersensitivity ea lithethefatsi,
Tse ling: khafetsa - mali a tsoang sebakeng sa kotlo, ka seoelo - ho tsoa mali ho tsoa leqeba la ho buoa, feberu.

Bokhachane le pelehi

Ho ea ka litaelo, Zilt ha e khothalletsoe hore e sebelisoe nakong ea kemolo, hobane ha ho na datha ea kliniki mabapi le ts'ebeliso ea Clopidogrel ho basali baimana. Liphuputso tsa liphoofolo ha lia senola litlamorao tse mpe tse tobileng kapa tse sa tobang tsa moriana ho ima, ho hlaha ha ngoana, ho tsoala ngoana, kapa khapang ea pelehi ea ngoana.

Ho lithuto tsa liteko tsa liphoofolo, ho ile ha fumaneha hore clopidogrel le metabolites ea eona li kenella ka lebese la matsoele, ka hona, haeba ho hlokahala hore ho sebelisoe Zilt ho basali ba anyesang, ho anyesa ho lokela ho emisoe.

Haeba ho na le bothata ba ho renal bo sa sebetseng

Ka tšebeliso e sa khaotseng ea Zilt ka tekanyo ea 75 mg ka letsatsi ho bakuli ba nang le ts'ebetso e matla ea masapo a mokokotlo (creatinine clearance - 5-15 ml / min), tekanyo ea khatello ea "platelet aggregation" e ne e le 25% e tlase ho feta tekanyo ea thibelo ea liplatelese tse ngata ho bapisoa le baithaopi ba phetseng hantle. Leha ho le joalo, ho eketsoa ha nako ea ho tsoa mali ho ne ho tšoana le ho baithaopi ba phetseng hantle ba neng ba amohela moriana ka tekanyetso ea 75 mg ka letsatsi. Mamello ea Zilt e nepahetse ka tsela e tšoanang ho bakuli bohle.

Ho sebelisana le lithethefatsi

Ka lebaka la kotsi e kholo ea ho tsoa mali, ha ho kgothaletswe ho fana ka lithethefatsi ka nako e le ngoe le warfarin, mme ha li kopantsoe le heparin le baemeli ba bang ba thrombolytic, tlhokomelo e khethehileng e lokela ho nkuoa.

Li-NSAID li eketsa kotsi ea ho ruruha le mali a tsoang ka mpeng.

Ha ho na ts'ebelisano e kholo ea kliniki e fumanoeng ka ts'ebeliso e le 'ngoe le atenolol, li-inhibitors tsa angiotensin-converting enzyme (ACE), lithethefatsi tse theolelang cholesterol ea mali, digoxin, nifedipine, phenobarbital, estrogens, cimetidine, theophylline.

Clopidogrel e kanna ea eketsa phello ea acetylsalicylic acid ho motsoako o kopaneng oa li-collagen. Ho sebelisana ha litlhare tsa lithethefatsi ka acetylsalicylic acid ho eketsa monyetla oa ho tsoa mali, ka hona ts'ebeliso ea motsoako ona e ka etsahala selemo sa 1 feela.

Ho monya ha clopidogrel ha ho amehe ke li-antacid.

Ho kopana le tolbutamide, phenytoin e eketsa boemo ba bona ba khatello ea mali maling a mali.

Litaba tsa Zilt ke: Lopirel, Clopidogrel, Clopidogrel-SZ, Plavix, Aggregal, Detromb, Cardutol, Clopidex, Clopilet, Listab 75, Deplatt-75, Cardogrel, Clopigrant, Lirta, Targetek, Plagril, Egithrombrel, Troken.

Litlhahlobo mabapi le Zilt

Bakuli ba arabela hantle ho moriana, ba sa ananele feela ts'ebetso ea ona, empa le theko e amohelehang (bapisoa le balekane ba bang ba theko e boima haholo). Ho latela maikutlo, Zilt e sebetsa kamora ho hlaseloa ke pelo le lits'ebetso tsa ho hlatsa. Bakuli ba hlokometse ntlafatso ea bophelo bo botle, ho felisoa ha litlhaselo tsa angina, le ho ba sieo ha lefu la mokokotlo le la mothapo.

Ka linako tse ling bakuli ba tletleba ka ho hlaha hoa litla-morao (urticaria, ho hema ka thata), empa haeba u tsoela pele kalafo, litla-morao tse sa rateheng li nyamela ka boyena kamora nakoana.

Theko ea Zilt libakeng tsa meriana

Ho fihla joale, litheko tse hakanyetsoang tsa Zilt libakeng tsa meriana li ka tsela e latelang:

matlapa a koahetsoeng ka filimi, 75 mg (14 likhomphutha. ka pakete e le 'ngoe) - li-ruble tse 470-530,
matlapa a koahetsoeng ka filimi, 75 mg (li-pcs tse 28 ka pakete) - li-ruble tse 830-1200,
matlapa a koahetsoeng ka filimi, 75 mg (likotoana tse 84 ka pakete) - li-ruble tse 1875 - 2030.

Suction

Kamora taolo e le 'ngoe le e pheta-phetoang ea molomo ka tekanyetso ea 75 mg ka letsatsi, clopidogrel e kenella ka potlako. Litekanyetso tse phahameng tsa kakaretso e phahameng ea "cmax" ea clopidogrel e sa fetoheng plasma ea mali (2.2-2.5 ng / ml kamora ho kenella ka tekanyetso e le 'ngoe ea 75 mg) li fihlella kamora metsotso e ka bang 45. Ho latela liphuputso tse entsoeng ka ho pepesetsoa ha methapo ea li-metabolite tsa clopidogrel, tekanyo ea ho koaloa e batla e le 50%.

Metabolism

Clopidogrel e kenngoe ka matla sebeteng. In vitro le vivo, clopidogrel e tšelisoa ka mekhoa e 'meli: ea pele e hokahanngoa le litheko mme e lebisa ho hydrolysis ka ho theha metabolite e sa sebetseng - derivative ea carboxylic acid (85% ea metabolites e potoloha), mme e ngoe e ts'oaroa ke li-isoenzymes tse fapaneng tsa cytochrome P450. Pele, clopidogrel e fetoloa metabolite e bohareng - 2-oxo-clopidogrel. Kamora metabolism ea morao-rao ea 2-oxo-clopidogrel e lebisa ho thehoeng hoa metabolite e sebetsang ea Clopidogrel - thiol e tsoang ho clopidogrel. Ka vitro, tsela ena e kopantsoe le isoenzymes CYP3A4, CYP2C19, CYP1A2 le CYP2B6. The thiol metabolite e sebetsang ea clopidogrel, e arotsoe ka vitro, e kenella ka potlako le ka mokhoa o sa fetoheng le li-receptor tsa platelet, li thibela bongata ba tsona.

Cmax ea metabolite e sebetsang ka plasma ea mali ka mor'a ho nka tekanyetso ea ho loading (300 mg) ea clopidogrel e phahame habeli ho Cmax kamora matsatsi a 4 a sebelisang clopidogrel ka lethal dose ea tlhokomelo (75 mg / letsatsi). Cmax e plasma ea mali e fihlella metsotso e ka bang 30-60 kamora ho sebelisa moriana.

Kamora ho kenella ha Clopidogrel e ngotsoeng ka 14C, hoo e ka bang 50% ea radioactivity eohle e epuoa ke liphio mme e ka ba 46% ke mala ka hare ho lihora tse 120 kamora ho hlohlona. Kamora taolo e le 'ngoe ea molomo ea Clopidogrel ka tekanyo ea 75 mg, halofo ea bophelo (T1 / 2) e batla e le lihora tse 6. T1 / 2 ea metabolite ea mantlha e sa sebetseng e potoloha ka har'a plasma ea mali kamora ts'ebeliso e le' ngoe le e pheta-phetoang ke lihora tse 8.

Thibelo ea mathata a atherothrombotic:

ho bakuli ba baholo ba nang le myocardial infarction (ho tloha matsatsing a 'maloa ho isa ho matsatsi a 35), ka lefu la ischemic (ho tloha ho matsatsi a 7 ho isa ho likhoeli tse 6), kapa ka tlhahlobo ea lefu la methapo ea methapo ea methapo,
ho bakuli ba baholo ba nang le lefu la ho hlobaetsana le hlooho ea methapo: ntle le sekhahla sa ST (ho sa tsitsinyehe ha angina kapa infarction ea myocardial ntle le Q wave), ho kenyelletsa le bakuli ba kileng ba ts'oaroa ke ho kenella ha coronary, hammoho le acetylsalicylic acid, e nang le ST sekhahla (acute myocardial infarction) ka kalafo ea lithethefatsi le monyetla oa phekolo ea thrombolytic, hammoho le acetylsalicylic acid.

Thibelo ea mathata a atherothrombotic le a thromboembolic, ho kenyelletsa le stroke, ka atrose ea fibrillation (atrial fibrillation)

Bakuli ba baholo ba nang le fibrillation ea atria (fibrillation ea atria), ba nang le bonyane kotsi e le 'ngoe bakeng sa nts'etsopele ea mathata a methapo, ha ba khone ho nka li-anticoagulants mme ba na le kotsi e tlase ea ho tsoa mali (hammoho le acetylsalicylic acid).

Acute coronary syndrome ntle le ho phahamisa karolo ea ST

Acute coronary syndrome e nang le sekhahla sa ST

Fibrillation ea Atrial (fibrillation ea atria)

Haeba mokuli a hlotsoe tekanyetso e latelang:

Haeba ho se ho fetile lihora tse 12 ka mor'a ho tlola tekanyetso e latelang, o lokela ho nka lethal dose e lahlehileng ea Zilt® hang-hang, 'me u noe tekanyo e latelang ka nako e tloaelehileng.
Haeba ho feta lihora tse 12 kamora ho tšollela lethal dose le latelang, lethal dose le hlahlamang le lokela ho nkuoa ka nako e tloaelehileng, athe tekanyetso ha ea lokela ho imena habeli.

Ts'ebetso ea mokokotlo e sa sebetseng

Sebelisa nakong ea bokhachane le pelehi

Liphuputso tsa liphoofolo li bontšitse hore li-clopidogrel le / kapa metabolites ea tsona li epuoa ka lebese la matsoele. Ka hona, haeba kalafo e nang le clopidogrel e hlokahala, ho kgothaletswa ho emisa ho anyesa.

Li-anticoagulants bakeng sa tsamaiso ea molomo

Ts'ebeliso e ts'oanang ea Clopidogrel le anticoagulants bakeng sa tsamaiso ea molomo e ka eketsa bongata ba ho tsoa mali, ka hona, ts'ebeliso ea motsoako ona ha e khothalletsoe.

Ts'ebeliso ea clopidogrel ka tekanyo ea 75 mg ka letsatsi ha e fetole li-pharmacokinetics tsa warfarin (karolo e ka tlase ea CYP2C9 isoenzyme) kapa karolelano ea machabeng e tloaelehileng (INR) ho bakuli ba fumanang kalafo ea nako e telele le warfarin. Leha ho le joalo, tšebeliso e tšoanang ka warfarin e eketsa kotsi ea ho tsoa mali ka lebaka la ts'usumetso e 'ngoe e ikemetseng ea tšilafalo ea mali. Ka hona, tlhokomeliso e lokela ho sebelisoa ha u ntse u sebelisa warfarin le clopidogrel.

Acetylsalicylic acid

Acetylsalicylic acid ha e ame ho thibeloa ha lintho tse ngata tse entsoeng ke plopidogrel tse hlahisoang ke ADP, empa li-Clopidogrel li hlahisa phello ea acetylsalicylic acid ho li-pollagen tse kenyellelitsoeng ka bongata. Leha ho le joalo, tsamaiso e tšoanang ea 500 mg ea acetylsalicylic acid habeli ka letsatsi bakeng sa letsatsi le le leng ha e atolle haholo nako ea ho tsoa mali e bakoang ke clopidogrel. Tšebelisano ea pharmacodynamic pakeng tsa clopidogrel le acetylsalicylic acid e kanna ea eketsa kotsi ea ho tsoa mali. Ha ho fanoa ka sena, tlhokomeliso e lokela ho sebelisoa ha u ntse u sebelisa meriana ena, leha ho le joalo lithutong tsa kliniki, bakuli ba nkile phekolo e kopaneng le clopidogrel le acetylsalicylic acid bakeng sa selemo se le seng.

Ho ea ka phuputso ea bongaka ho batho ba phetseng hantle, ha ho nka clopidogrel, ho ne ho se na lebaka la ho fetola tekanyetso ea heparin, 'me phello ea anticoagulant ea heparin ha ea fetoha. Ho sebelisoa ha heparin ka nako e le 'ngoe ha hoa ka ha ama khatello ea khatello ea liplatele ka Clopidogrel. Mohlomong tšebelisano ea pharmacodynamic lipakeng tsa clopidogrel le heparin, e lebisa kotsing e kholo ea ho tsoa mali. Ka hona, ts'ebeliso e tšoanang ea meriana ena e hloka tlhokomeliso.

Supombolytics

Polokeho ea tšebeliso ea nako e le 'ngoe ea clopidogrel, fibrin-itseng kapa fibrin e ikhethang ea thrombolytics le heparin e ile ea hlahlojoa ho bakuli ba nang le infarction ea myocardial e mpe. Monyetla oa ho tsoa mali ka mokhoa o ikhethang o ne o bapisoa le ts'ebeliso ea nako e le 'ngoe ea thrombolytics, heparin e nang le acetylsalicylic acid.

Lithethefatsi tse sa sebetseng ka matla ho felisang tšoaetso (NSAIDs)

Ho latela lipatlisiso tsa bongaka tse amang baithaopi ba phetseng hantle, tšebeliso ea nako e tšoanang ea Clopidogrel le naproxen e ile ea eketsa ho tsoa mali ka mpeng. Leha ho le joalo, ka lebaka la khaello ea lithuto mabapi le ho sebelisana le li-NSAID tse ling hajoale, ha ho tsejoe hore na menyetla ea ho tsoa mali e ka mpefala ha e sebelisoa hammoho le li-NSAID tse ling. Ka hona, kalafo e tšoanang ea NSAIDs, ho kenyelletsa COX-2 inhibitors, le clopidogrel e lokela ho etsoa ka hloko (bona karolo ea "Litaelo tse Khethehileng").

CYP2C19 Isoenzyme Inhibitors

Clopidogrel e tšelisoa 'moho ho hlahisa metabolite ea eona e sebetsang, ka karolo e' ngoe tlas'a tšusumetso ea CYP2C19 isoenzyme. Ka hona, lithethefatsi tse thibelang isoenzyme ena li ka baka ho fokotseha ha khatello ea metabolite e sebetsang ea clopidogrel. Bohlokoa ba bongaka ba tšebelisano ena ha bo tsejoe. Tšebeliso e ts'oanang le li-inhibitors tse nang le matla kapa tse leka-lekaneng tsa CYP2C19 isoenzyme li lokela ho qojoa. Li-inhibitors tsa CYP2C19 isoenzyme li kenyelletsa omeprazole le esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine le chloramphenicol.

Proton inhibitors

Ts'ebeliso ea omeprazole ka tekanyo ea 80 mg hang hang ka letsatsi ka nako e le ngoe le clopidogrel kapa nako ea phomolo ea lihora tse 12 pakeng tsa ho sebelisa lithethefatsi tse peli e fokotsitse boleng ba tlhaiso ea systemic (AUC) ea metabolite e sebetsang ea Clopidogrel ka 45% (kamora ho nka lethal dose ea Clopidogrel) le 40% (kamora ho nka tekanyetso ea tlhokomelo. litekanyetso tsa clopidogrel). Ho fokotseha ha AUC ea metabolite e sebetsang ea Clopidogrel ho amana le ho fokotseha ha tekanyo ea thibelo ea liphatlalatso tsa mokokotlo (39% kamora ho nka lethal dose ea clopidogrel le 21% kamora ho nka tekanyetso ea tlhokomelo ea clopidogrel). Ho khothalletsoa tšebelisano e tšoanang ea clopidogrel le esomeprazole. Thutong ea boithuto le ea bongaka, datha tse hanyetsanang mabapi le lipontšo tsa bongaka tsa ts'ebetso ea pelo mabapi le ts'ebelisano ena ea pharmacokinetic / pharmacodynamic li tlalehiloe. Tšebeliso e kopanetsoeng le omeprazole kapa esomeprazole e lokela ho qojoa.