Clopidogrel teva

Gulu la mankhwala

Othandizira antithrombotic. Ma antiplatelet. Code ATX B01A C04.

Kupewa kwa atherothrombosis mwa akulu

• Odwala omwe adayamba kudwala matendawa (kuyambika kwa mankhwalawa masiku ochepa, koma osadutsa masiku 35 atayamba), matenda a ischemic (kuyamba kwa mankhwala ndi masiku 7, koma osapitilira miyezi 6 atadwala mitsempha yodutsa (kuwonongeka kwa mitsempha ndi ma atherothrombosis a ziwiya zam'munsi),
• Odwala omwe ali ndi pachimake coronary syndrome (ACS):
• Ndi pachimake coronary syndrome popanda kukwera kwa gawo (osakhazikika angina kapena myocardial infarction popanda Q wave), kuphatikiza pa odwala omwe adakumana ndi kusokonezeka mkati mwa percutaneous coronary angioplasty, limodzi ndi acetylsalicylic acid (ASA)
• ndi pachimake myocardial infarction ndi gawo gawo la ST, limodzi ndi acetylsalicylic acid (odwala omwe amalandila mankhwala okhazikika omwe akuwonetsedwa chithandizo cha thrombolytic).

Kupewa kwa zochitika za atherothrombotic ndi thromboembolic mu atria fibrillation:

• Clopidogrel osakanikirana ndi ASA akuwonetsedwa mwa odwala akuluakulu omwe ali ndi fibrillation ya atgency, omwe ali ndi vuto limodzi pangozi ya zochitika zamankhwala, momwe mumakhala zotsutsana ndi chithandizo cha vitamini K antagonists (AVK) komanso omwe ali ndi chiopsezo chochepa cha magazi, pofuna kupewa zochitika za atherothrombotic ndi thromboembolic kuphatikizapo sitiroko.

Mlingo ndi makonzedwe

Akuluakulu, kuphatikiza odwala okalamba. Clopidogrel ndi mankhwala 75 mg 1 nthawi patsiku, ngakhale kudya.

Chithandizo cha Clopidogrel odwala ACS yopanda ST gawo yokweza (osakhazikika angina pectoris kapena infrction ya myocardial yopanda Q wave pa ECG) amayamba ndi muyeso umodzi wokweza 300 mg, kenaka pitilizani pa mlingo wa 75 mg kamodzi patsiku (ndi acetylsalicylic acid (ASA) pa mlingo wa 75 325 mg / tsiku. Popeza kugwiritsa ntchito milingo yapamwamba ya ASA kumawonjezera mwayi wokhetsa magazi, ndikulimbikitsidwa kuti musapitirire mlingo wa acetylsalicylic acid wa 100 mg. Kutalika kokwanira kwa chithandizo sikunakhazikitsidwe. Phindu logwiritsa ntchito mankhwalawa mpaka miyezi 12 idanenedwa, ndipo kuchuluka kwake kumawonedwa pambuyo pa miyezi itatu ya chithandizo.

Odwala ndi pachimake myocardial infarction ndi ST gawo kukweza clopidogrel ndi mankhwala 75 mg kamodzi patsiku, kuyambira limodzi lokha lomwe limaperekedwa 300 mg molumikizana ndi ASA, mankhwala okhala ndi thrombolytic kapena osapindika. Chithandizo cha odwala okalamba osaposa zaka 75 chimayamba popanda kukweza mlingo wa clopidogrel. Kuphatikiza mankhwalawa kuyenera kuyambikanso atangoyamba kumene zizindikiro ndipo akuyenera kupitiliza kwa milungu inayi. Ubwino wogwiritsa ntchito kuphatikizika kwa clopidogrel ndi ASA kwa masabata opitilira anayi ndi matenda awa sizinaphunzire.

Kwa odwala omwe ali ndi fibrillation ya atrial, clopidogrel amagwiritsidwa ntchito limodzi mu 75 mg. Pamodzi ndi clopidogrel, kugwiritsa ntchito ASA kuyenera kuyambitsidwa ndikupitilizidwa (pa mlingo wa 75-100 mg patsiku).

Ngati mwasowa mlingo:

• Wochepera 12:00 wadutsa kuyambira pomwe anafunika kumwa mlingo wotsatira, wodwalayo atenge kumwa nthawi yomweyo, ndipo mlingo wotsatira uyenera kumwedwa nthawi yomweyo.
• Ngati zidutsa kupitirira 12:00, wodwalayo amwe mlingo wotsatira nthawi yotsatira koma osawonjezera kawiri pa mankhwalawo pofuna kulipiritsa mlingo womwe mwasowa.

Kulephera kwina . Zowonjezera zothandizira kugwiritsa ntchito mankhwalawa kwa odwala omwe ali ndi vuto la impso ndizochepa.

Kulephera kwa chiwindi . Zowonjezera zothandizira kugwiritsa ntchito mankhwalawa kwa odwala omwe ali ndi chiwindi chambiri matenda ndi kuthekera kwa hemorrhagic diathesis ndizochepa.

Zotsatira zoyipa

Zinanenedwa kuti kutaya magazi kunali kovutirapo ndipo kawirikawiri kumachitika mwezi woyamba wa chithandizo.

Zotsatira zoyipa zimagawidwa pakati pa ziwalo, pafupipafupi momwe zimakhalapo zimafotokozedwa motere: kawirikawiri (kuyambira ³ 1/100 mpaka ≤ 1/10), mokulira (kuyambira ³ 1/1000 mpaka ≤ 1/100), kawirikawiri (kuyambira ³ 1/10 000 mpaka ≤ 1/1000), chosowa kwambiri (zidziwitso Amvera

Mlingo

Mapiritsi okhala ndi mafilimu 75 mg

Piritsi limodzi lili

yogwira mankhwala: clopidogrel hydrosulfate 97.857 mg,

zofanana ndi clopidogrel 75,00 mg

zotupa: lactose monohydrate (200 mauna), microcrystalline cellulose (Avicel PH 101), hydroxypropyl cellulose (Klucel LF), microcrystalline cellulose (Avicel PH 112), crospovidone (Collidon CL), hydrogenated masamba mtundu wa I (Sterotex-Drite) sodium hydrate. lauryl sulfate

kapangidwe kake: lactose monohydrate, hypromellose 15 cP, titanium dioxide (E171), polyethylene glycol 4000, iron oxide ofiira (E172), iron oxide chikasu (E172), indigotine (E 132, indigo carmine aluminium varnish FD&C buluyi Na. 2)

Mapiritsiwa ndi ophatikizidwa ndi film kuchokera ku pinki yowala kupita ku pinki, wojambula-kapangidwe kake, wolemba "93" mbali imodzi ndi "7314" mbali inayo.

Mankhwala

Pambuyo pakamwa, clopidogrel imatengedwa mwachangu kuchokera m'mimba. Wapakati pachimake plasma osasintha osasintha osasintha (pafupifupi 2,2,5,5 ng / ml pambuyo pa gawo limodzi la 75 mg) amafika mphindi 45 atatha kumwa mankhwalawa. Mafuta odziwikapo mtima ochokera ku matenda a impopidogrel metabolites ndi 50%.

Clopidogrel ndi metabolite yake yayikulu (yosagwira) yomwe imazungulira m'magazi, imapanga kulumikizana kosinthika ndi mapuloteni a plasma a anthu (98% ndi 94%, motsatana). Chomangirira sichimadzaza pamitundu yambiri.

Clopidogrel imadutsa kwambiri chiwindi. Clopidogrel imapukusidwa m'njira ziwiri zazikulu: imodzi imayendetsedwa ndi ma esterases ndikupanga hydrolysis ndikupanga kochokera mu carboxylic acid (85% ya metabolites m'magazi), inayo imayesedwa ndi ma Pto50 ambiri a cytochromes. Choyamba, clopidogrel imapangidwira kwa yapakatikati metabolite, 2-oxo-clopidogrel. Pambuyo kagayidwe kachakudya kagayidwe kachakudya 2 - oxo-clopidogrel kumabweretsa mapangidwe yogwira metabolite, thiol yotengera Clopidogrel. Njira ya metabolic iyi imayendetsedwa ndi CYP3A4, CYP2C19, CYP1A2 ndi CYP2B6. The yogwira thiol metabolite imamangirira mwachangu komanso mosasinthika kwa mapulateleti, motero imalepheretsa kuphatikizika kwa maselo ambiri.

Cmax yogwira metabolite imachulukitsa 2, onse atatenga limodzi la mankhwala a clopidogrel 300 mg, ndipo atatha kumwa mankhwalawa 75 mg kwa masiku anayi. Cmax imawonedwa pafupifupi mphindi 30-60 pambuyo pa kuperekedwa.

Mukatenga clopidogrel, pafupifupi 50% imachotsedwa mu mkodzo ndipo pafupifupi 46% ndi ndowe mkati mwa maola 120 pambuyo pa kuwongolera. Pambuyo pakamwa limodzi lokha la 75 mg, kuthetseratu theka la moyo wa clopidogrel pafupifupi maola 6. Hafu ya moyo wa mainite (osagwira) metabolite yozungulira m'magazi ndi maora 8 pambuyo pa kayendetsedwe kamodzi komanso mobwerezabwereza.

CYP2C19 imathandizira popanga onse yogwira metabolite komanso yapakatikati metabolite, 2-oxo-clopidogrel. Ma pharmacokinetics ndi antiplatelet zotsatira za metabolite yogwira ya clopidogrel zimasiyana malinga ndi mtundu wa CYP2C19 genotype.

CYP2C19 * 1 allele imafanana ndi metabolism yogwira ntchito mokwanira, pomwe ma CYP2C19 * 2 ndi CYP2C19 * 3 maulendowa sagwira ntchito. Nkhaniyi ya CYP2C19 * 2 ndi CYP2C19 * 3 imafotokoza ambiri mwa omwe amachepetsa ntchito ku Europe (85%) ndi ku Asia (99%) metabolites. Zovomerezeka zina zomwe zimagwirizanitsidwa ndi kuchepa kapena kuchepa kwa metabolism sizachilendo ndipo zimaphatikizapo CYP2C19 * 4, * 5, * 6, * 7 ndi * 8. Kufalikira kwa CYP2C19, zomwe zimapangitsa kuti CYP2C19 ichepetse komanso pang'ono pang'onopang'ono, zinali zosiyana kutengera mtundu / fuko. Zambiri zosakwanira zolembedwa zilipo kwa anthu aku Asia, zomwe sizitilola kuti tiwone zotsatira za CYP2C19 genotyping pa zotsatira zamankhwala.

Wodwala wokhala ndi mawonekedwe a metabolizer wodekha amakhala ndi zofunikira ziwiri zopanda ntchito, monga tafotokozera pamwambapa. Kukula kwa genotype kwa metabolite yapang'onopang'ono ya CYP2C19 kuli pafupifupi 2% kwa azungu, 4% ya mpikisano waku Africa komanso 14% yaku China. Pali mayeso oti adziwe mtundu wa CYP2C19 genotype.

Panalibe kusiyana kwakukulu paziwonetsero za metabolite yogwira komanso kuponderezedwa kwapakati pa kuphatikizika kwa maselo ambiri (PAT) pakati pa ultrafast, kudya mwachangu komanso kwapakati. Mu metabolites wodekha, kuwonetsa kwa metabolite yogwira ntchito kumatsika ndi 63-71% poyerekeza ndi metabol metabol. Pambuyo pakugwiritsa ntchito njira ya 300 mg / 75 mg yeniyeni, kuchepa kwa mayankho a antiplatelet pang'onopang'ono pamawonedwe, kumadziwika, PAT (5 μM ADP) kukhala 24% (maola 24) ndi 37% (tsiku 5) poyerekeza 39% PAT (maola 24) ) ndi 58% (tsiku 5) yama metabolites othamanga ndi 37% (maola 24) ndi 60% (tsiku 5) ya ma metabolidal apakati. Pamene ma metabolites odekha amapezeka mu 600 mg / 150 mg regimen, kuwonekera kwa metabolite yogwira ndi kwakukulu kuposa momwe zimakhalira ndi 300 mg / 75 mg regimen. Kuphatikiza apo, PAT ndi 32% (maora 24) ndi 61% (tsiku 5), zomwe ndizochulukirapo kuposa zomwe zimapangidwira pang'onopang'ono zomwe zinali pa mauligalamu 300 mg / 75 mg, koma zofanana ndi magulu ena a ma CYP2C19 metabolizer omwe ali pa 300 mg / 75 regimen mg Mndandanda woyenera wa odwala awa sunakhazikitsidwe.

Kuwonetsedwa kwa metabolite yogwira kumatsitsidwa ndi 28% mu ma metabolidal apakati komanso ndi 72% pang'onopang'ono metabolizer, pomwe kutsindikiza kwa kupatsidwa zinthu za m'magazi (5 μM ADP) kumachepa ndikusiyana PAT ya 5.9% ndi 21.4%, motsatana, poyerekeza ndi kuthamanga ma processor.

The pharmacokinetics of the metabolite yogwira ya clopidogrel mu awa (omwe ali ndi vuto la chiwindi ndi ntchito ya impso) kuchuluka kwapadera sikudziwika.

Matenda aimpso

Pambuyo Mlingo wambiri wa clopidogrel pa 75 mg patsiku kwa odwala omwe ali ndi vuto lalikulu la impso (creatinine chilolezo kuyambira 5 mpaka 15 ml / min), kutsutsana kwa maselo othandiza magazi kuundana chifukwa cha ADP (adenosine diphosphate) kumakhala kofooka (25%) kuposa m'maphunziro abwino, komabe, kuchuluka kwa nthawi magazi ndi ofanana ndi nthawi yotaya magazi m'maphunziro athanzi omwe adalandira 75 mg ya clopidogrel patsiku. Kuphatikiza apo, pali kulekerera kwabwino kwa odwala onse.

Kuwonongeka kwa chiwindi

Pambuyo Mlingo wa clopidogrel mobwerezabwereza 75 mg pa tsiku kwa masiku 10 kwa odwala omwe ali ndi vuto lalikulu la chiwindi, chophatikizira kuphatikizana kwa maselo ambiri chifukwa cha ADP ndi ofanana ndi maphunziro abwino. Kutalika kwapakati kwakutulutsa magazi m'magulu onse awiriwa kumasinthanso.

Clopidogrel ndiwotsogola kwa chinthu chomwe chimagwira, chimodzi mwazinthu zopanga metabolites zomwe ndi zoletsa za kuphatikizika kwa maselo.Clopidogrel imapangidwa ndi ma enzymes a CYP2C19, zomwe zimapangitsa kuti pakhale metabolite yogwira yomwe imalepheretsa kuphatikizika kwa maselo ambiri. Yogwira clopidogrel metabolite mosamala imalepheretsa kumangiriza kwa adenosine diphosphate (ADP) ku mapuloteni othandizira a P2Y12 komanso kuyambitsa kwa GPIIb / IIIa glycoprotein zovuta chifukwa cha ADP, potero kuteteza kuphatikizana kwa mapulateleti. Chifukwa chosasinthika, zomangamanga zimawonongeka kwa moyo wawo wonse (pafupifupi masiku 7-10), ndipo magwiridwe antchito amamasulidwe amabwezeretsedwa pamlingo wofanana ndi kuzungulira kwamapulogalamu. Kuphatikizana kwa mapulateleti oyambitsidwa ndi agonists ena osakhala a ADP kumathandizidwanso ndikuletsa kukwezedwa kwa mapulogalamu am'magulu a pulatifomu poyerekeza ndi ADP yotulutsidwa.

Popeza metabolite yogwira imapangidwa pogwiritsa ntchito ma enzymes a CYP450, ena omwe ndi ma polymorphic kapena oponderezedwa ndi mankhwala ena othandizira, si odwala onse omwe ali ndi digirii yolekerera.

Mlingo wobwereza wa 75 mg patsiku kuyambira tsiku loyamba kumabweretsa chiwopsezo chachikulu cha kuphatikizika kwa maselo ambiri chifukwa cha ADP. Mphamvu yoletsa kukwera imakulirakulira pang'onopang'ono ndikufika pamitundu yofananira masiku 3-7. Pa gawo lofanana, kuchuluka kwa zoletsa kumawonedwa pamtundu wa 75 mg patsiku ndipo umachokera 40% mpaka 60%. Kuphatikizana kwa pulasitiki ndi nthawi yotuluka magazi pang'onopang'ono imabweleranso ku nthawi yake yoyambayo, nthawi zambiri masiku 5 atachotsedwa.

Kupewa kwa zochitika za atherothrombotic:

- odwala ndi myocardial infarction (kuyambira masiku angapo mpaka

Mlingo ndi makonzedwe

Clopidogrel-Teva amalembedwa pakamwa mosasamala za kudya.

Kwa achikulire ndi odwala okalamba, clopidogrel-Teva amapatsidwa mlingo umodzi wa 75 mg.

Mu pachimake coronary syndrome popanda kukweza gawo la ST (osakhazikika angina kapena myocardial infarction popanda mafunde a Q), mankhwalawa ndi mankhwala omwe amapezeka ndi 300 mg. Mlingo wokonza ndi 75 mg patsiku (kuphatikiza ndi acetylsalicylic acid pa 75 7525 mg / tsiku) kwa miyezi 12. Kwambiri achire zotsatira zimawonedwa pambuyo 3 miyezi. Sitikulimbikitsidwa kupitilira muyeso wa acetylsalicylic acid woposa 100 mg, chifukwa chowonjezera chotupa.

Mu kulowetsedwa pachimake myocardial ndi kuwonjezeka gawo la ST, mankhwalawa amadziwitsidwa pa mlingo wa 75 mg patsiku (osakanikirana ndi acetylsalicylic acid) kuyambira ndi mtundu umodzi wa 300 mg, wokhala ndi mankhwala osapindika kapena opanda thrombolytic. Odwala azaka zopitilira 75, chithandizo cha Clopidogrel-Teva chikuchitika popanda kugwiritsa ntchito mlingo umodzi wokweza. Kuphatikiza mankhwalawa kuyenera kuyambika posachedwa pambuyo pa kuyamba kwa zizindikiro ndikupitilira kwa milungu inayi.

Ndi fibrillation ya atgency, mankhwalawa amadziwikiridwa ngati gawo limodzi la 75 mg, kuphatikiza acetylsalicylic acid 75-100 mg patsiku.

Ngati mungadumphe kumwa mankhwala osakwana maola 12 kuchokera nthawi yanthawi, wodwalayo amwe mankhwalawo nthawi yomweyo, kenaka amwe mlingo wotsatira panthawi yokhazikika. Ngati maola opitilira 12 adatha, wodwalayo amatenga mankhwalawa panthawi yokhazikika, sayenera kumwa kawiri.

Matenda aimpso

Chithandizo cha Clopidogrel mwa odwala omwe ali ndi vuto laimpso ndilochepa. Chifukwa chake, pankhani ya odwala otere, mankhwalawa ayenera kugwiritsidwa ntchito mosamala.

Kuwonongeka kwa chiwindi

Zochitika kugwiritsa ntchito mankhwalawa odwala omwe ali ndi vuto la chiwindi, zolimbitsa thupi, zomwe zimapangitsa kuti hemorrhagic diathesis, ikhale yochepa. Pankhani imeneyi, mwa anthuwa, mankhwalawa ayenera kugwiritsidwa ntchito mosamala.

Zotsatira zoyipa

Kuyamwa ndi njira yodziwika yomwe imachitika pazolemba zamankhwala komanso nthawi yotsatsa malonda, pomwe idalembedwa makamaka mwezi woyamba wa chithandizo.

Zoyipa zomwe zalembedwa m'mayesero azachipatala kapena omwe akunenedwa mwatsatanetsatane zalembedwa pansipa.

Contraindication

- Hypersensitivity to the yogwira mankhwala kapena zigawo zikuluzikulu za mankhwala

- kukanika kwambiri kwa chiwindi

- magazi akutupa kwambiri (zilonda zam'mimba, zotupa za intracranial)

- galactose tsankho, Lapp lactase akusowa kapena shuga-galactose malabsorption

- mimba ndi mkaka wa m`mawere

- ana osakwana zaka 18

Zochita zamankhwala osokoneza bongo

Ma anticoagulants am'kamwa: kugwiritsa ntchito nthawi yomweyo clopidogrel ndi anticoagulants osavomerezeka sikulimbikitsidwa, popeza kuphatikiza kumeneku kumatha kuwonjezera magazi. Ngakhale kuti kutenga 75 mg ya clopidogrel patsiku sikusintha ma pharmacokinetics a S-warfarin kapena chiyezo chofananira padziko lonse lapansi (INR) mwa odwala omwe akutenga warfarin kwa nthawi yayitali, kugwiritsa ntchito nthawi yomweyo clopidogrel ndi warfarin kumawonjezera chiopsezo chakutuluka kwa magazi chifukwa cha zonse ziwiri za hemostasis mankhwala.

Glycoprotein IIb / IIIa zoletsa: clopidogrel iyenera kugwiritsidwa ntchito mosamala mu odwala omwe akutsatira IIb / IIIa glycoprotein inhibitors.

Acetylsalicylic acid (ASA): ASA sikusintha zoletsa zomwe zimapangitsa kuti magazi azikhala am'madzi, koma Clopidogrel imawonjezera mphamvu ya ASA pakaphatikizidwe ka mapulateleti oyambitsidwa ndi collagen. Komabe, makonzedwe omwewo a ASA pa 500 mg kawiri patsiku tsiku lonse sayambitsa kuchuluka kwa magazi nthawi yayitali chifukwa cha kubanika kwa magazi. Pakati pa clopidogrel ndi acetylsalicylic acid, kuyanjana kwa pharmacodynamic ndikotheka, komwe kumayambitsa chiopsezo chowonjezereka cha magazi. Chifukwa chake, kugwiritsa ntchito mankhwalawa pa mankhwalawa kuyenera kuchitika mosamala. Komabe, clopidogrel ndi ASA zimayikidwa limodzi mpaka chaka chimodzi.

Heparin: clopidogrel sikutanthauza kusintha kwa heparin kapena sikukuwononga zotsatira za heparin pakuwundana kwa magazi. Kugwiritsira ntchito kwa nthawi imodzi kwa heparin sikukhudza kulepheretsa kuphatikizana kwa maselo am'mimba chifukwa cha clopidogrel. Pakati pa clopidogrel ndi heparin, kuyanjana kwa pharmacodynamic ndikotheka, zomwe zimayambitsa chiopsezo chowonjezereka cha magazi. Chifukwa chake, kugwiritsa ntchito mankhwalawa pa mankhwalawa kuyenera kuchitika mosamala.

Othandizira a thrombolytic: chitetezo cha mgwirizano wa clopidogrel wokhala ndi ma fibrin-enieni komanso osagwirizana ndi fibrin-enieni a thrombolytic othandizira ndi heparins adawerengera odwala omwe ali ndi infralate ya myocardial infarction. Kutuluka kwa magazi kwakanthawi kwakanthawi kumakhalabe kofanana ndi komwe kumatumizidwa ndi ma thrombolytic othandizira komanso heparin limodzi ndi ASA.

Mankhwala osagwirizana ndi ma antisteroidal (NSAIDs): kuphatikiza magazi ndi mankhwalawa kumawonjezera kuchepa kwa magazi kuchokera m'mimba. Komabe, chifukwa cha kuchepa kwa maphunziro azachipatala okwanira pakukhudzana ndi ma NSAID ena, pakadali pano sizikudziwika ngati ngozi yowonjezereka ya kutuluka kwa m'mimba imadziwika ndi ma NSAID onse. Chifukwa chake, kugwiritsa ntchito nthawi yomweyo kwa NSAIDs (kuphatikiza COX-2 zoletsa) ndi clopidogrel kumafuna kusamala.

Mankhwala enanso: popeza clopidogrel imapukusidwa ku metabolite yake yogwiritsa ntchito CYP2C19, zikuyembekezeredwa kuti kugwiritsa ntchito mankhwala omwe amachepetsa ntchito ya enzyme imeneyi kudzapangitsa kuchepa kwa chidwi cha mankhwala a metabolite a clopidogrel. Kukula kwakukhudzana kwachithandizo kumeneku sikumveka bwino.Monga kusamala, kugwiritsa ntchito mankhwala omwe amachepetsa CYP2C19 kuyenera kutayidwa.

Mankhwala omwe amaletsa CYP2C19 akuphatikiza omeprazole ndi esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine ndi chloramphenicol.

Proton Pump Inhibitors (PPIs):

Omeprazole pa mlingo wa 80 mg kamodzi patsiku, amatengedwa nthawi yomweyo ndi clopidogrel, kapena ndi maola 12 pakati pamiyeso ya mankhwala awiri, amachepetsa kuwonetsa kwa metabolite yogwira ndi 45% (mlingo wokweza) ndi 40% (mlingo wokonzanso). Kutsika kochokera 39% (muyezo wokweza) ndi 21% (muyeso wokonzanso) kumalumikizidwa ndi kuchepa kwa kuponderezana kwa kuphatikizika kwa maplatelet. Esomeprazole, amatengedwa chimodzimodzi ndi clopidogrel, amayembekezeranso kuchepetsa kuwonetsa kwa metabolite yogwira. Monga kusamala, omeprazole kapena esomeprazole sayenera kugwiritsidwa ntchito nthawi yomweyo ndi clopidogrel.

Kuchepa kocheperako kwa metabolite kumawonekera pathupi la pantoprazole ndi lansoprazole.

Plasma wozungulira yogwira metabolite yafupika ndi 20% (okweza mlingo) ndi 14% (kukonzanso mlingo) pa mankhwala ndi pantoprazole muyezo wa 80 mg kamodzi patsiku. Izi zimayendera limodzi ndi kuchepa kwapakati pa kuphatikizika kwa maplatelet ndi 15% ndi 11%, motero. Izi zikutanthauza kuti clopidogrel angagwiritsidwe ntchito ndi pantoprazole.

Palibe umboni kuti mankhwala ena am'mimba otsitsa asidi, monga H2 receptor blockers (kupatula cimetidine, yemwe ndi CYP2C19 inhibitor) kapena maantacid, amasokoneza ntchito ya antiopatelet ya clopidogrel.

Mankhwala ena:

Palibe zofunika zamankhwala kuphatikizana ndi clopidogrel ndi atenolol kapena nifedipine kapena ndi zinthu zonsezi. Kugwiritsa ntchito pamodzi kwa phenobarbital kapena estrogen sikukhudzanso kwambiri zochita za pharmacodynamic za clopidogrel.

Ma pharmacokinetics a digoxin ndi theophylline sasintha pogwiritsa ntchito nthawi yomweyo ndi clopidogrel.

Maantacidus sasintha kuchuluka kwa mayamwidwe a clopidogrel.

Phenytoin ndi tolbutamide, omwe amapangidwa pogwiritsa ntchito CYP2C9, angagwiritsidwe ntchito mosavomerezeka ndi clopidogrel.

Kafukufuku wokhudzana ndi kuyanjana kwa clopidogrel ndi mankhwala ena, omwe nthawi zambiri amaperekedwa kwa odwala omwe ali ndi atherothrombosis (kuwonjezera pa mankhwala omwe takambirana pamwambapa), sanachitike. Komabe, kwa odwala omwe akuchita nawo mayesero a Clopidogrel omwe adamwa, limodzi ndi mankhwala osokoneza bongo a Clopidogrel, palibenso zovuta zina zoyipa. Mankhwalawa akuphatikizapo diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), calcium antagonists, cholesterol kuchepetsa mankhwala, corodary vasodilators, antidiabetic mankhwala (kuphatikiza insulin), antiepileptic mankhwala, komanso blockers a GPII Zolandila za IIIa.

Malangizo apadera

Kupuma komanso matenda a hematological

Chifukwa chakuchepa kwa magazi komanso kusintha kwatsoka kwa mankhwalawa panthawi ya chithandizo, ngati zizindikiro zamankhwala zikusonyeza kuti kutaya magazi, kuyezetsa magazi ndi / kapena kuyesa kwina koyenera kuyenera kuchitidwa nthawi yomweyo. Monga othandizira ena a antiplatelet, clopidogrel iyenera kugwiritsidwa ntchito mosamala ngati odwala omwe ali pachiwopsezo cha kuchuluka kwa magazi okhudzana ndi kuvulala, maopaleshoni kapena zina zodwala, komanso kwa odwala omwe amachitidwa ndi ASA, heparin, IIb glycoprotein inhibitors / IIIa kapena mankhwala osokoneza bongo omwe amaletsa kutupa (NSAIDs), kuphatikizapo COX-2 inhibitors. Odwala amayenera kuwunikidwa mosamala kuti awone ngati ali ndi magazi aliwonse, kuphatikizapo kutuluka magazi zamatsenga, makamaka m'milungu yoyamba yamankhwala komanso / kapena pambuyo pochita opaleshoni yamtima kapena ya opaleshoni.Kugwiritsira ntchito nthawi yomweyo ya clopidogrel ndi anticoagulants sikulimbikitsidwa, chifukwa izi zimatha kuwonjezera magazi.

Ngati wodwala wachita opaleshoni yosankhidwa, ndipo mphamvu ya antiplatelet ndi yosafunikira kwakanthawi, clopidogrel iyenera kusiyidwa masiku 7 asanafike opaleshoni. Opaleshoni iliyonse isanakonzekere komanso kumwa mankhwala aliwonse atsopano, odwala ayenera kuchenjeza akatswiri azachipatala komanso kuti adwala.

Clopidogrel imachulukitsa nthawi yowukha magazi ndipo iyenera kugwiritsidwa ntchito mosamala odwala omwe ali ndi vuto la pathological lomwe limatulutsa magazi (makamaka m'mimba ndi intraocular).

Odwala ayenera kudziwitsidwa kuti akamatenga Clopidogrel-Teva (yekha kapena osakanikirana ndi ASA), zimatenga nthawi yayitali kuti magazi athetse, ndikuwadziwitsa adokotala ngati akumana ndi magazi osayembekezeka (mwa malo kapena nthawi) kutuluka kwa magazi .

Thrombotic Thrombocytopenic Purpura (TTP)

Osowa kwambiri, milandu ya thrombotic thrombocytopenic purpura (TTP) imanenedwa pambuyo pa kugwiritsa ntchito mankhwalawa Clopidogrel-Teva, ndipo nthawi zina atakhala kanthawi kochepa. Amadziwika ndi thrombocytopenia ndi microangiopathic hemolytic anemia, limodzi ndi kusintha kwa mitsempha, kukanika kwa impso, kapena kutentha thupi. TTP ndi chiopsezo cha moyo chomwe chimafuna chithandizo chamanthawi yomweyo, kuphatikizapo plasmapheresis.

Zinanenedwa kuti kutenga clopidogrel kumabweretsa chitukuko cha hemophilia. Kuthekera kotenga hemophilia kuyenera kuganiziridwa ndi kuwonjezeka kwakutalikirana kwa anakanthidwa gawo la thromboplastin nthawi (APTT), kapena osatuluka magazi. Chithandizo cha odwala omwe ali ndi chitsimikiziro chowonetsa kuti ali ndi hemophilia ndikuwunika momwe alili ayenera kuchitika ndi akatswiri, ndipo clopidogrel iyenera kusiyidwa.

Posachedwa ischemic stroke

Chifukwa cha kusowa kwa chidziwitso, mankhwalawa sangathenso kuvomerezeka masiku 7 atadwala kwambiri.

Cytochrome P450 2C19 (CYP2C19)

Pharmacogenetics: Panthawi ya odwala omwe amachedwa CYP2C19 metabolites, clopidogrel amakhala ndi metabolites yochepa kwambiri pamankhwala olimbikitsidwa, ndipo amathandizira pang'onopang'ono kugwira ntchito kwa mapulogalamu. Pali mayeso oti adziwe CYP2C19 genotype mwa odwala.

Popeza kupangidwa kwa metabolop yogwira clopidogrel metabolites, mwanjira imodzi, ndi kutenga nawo gawo kwa CYP2C19, zikuyembekezeka kuti kugwiritsa ntchito mankhwala omwe amalepheretsa zochita za enzymeyi kuyambitsa kutsika kwa kuchuluka kwa ma metabolites amenewa. Kufunika kwachipatala pakuyanjanaku sikunadziwikebe. Monga kusamala, kugwiritsa ntchito ma inhibitors a CYP2C19 olimba kapena ocheperako sikuvomerezeka nthawi yomweyo ndi mankhwalawa.

Thupi lawo siligwirizana

Popeza kuphatikizanso kwodutsa komwe kumayambitsa kukhudzana kwa thupi kumanenedwa pakati pa thienopyridines, ziyenera kuwunika ngati wodwalayo ali ndi mbiri ya hypersensitivity kwa thienopyridine ena, monga ticlopidine ndi prasugrel. Odwala omwe ali ndi mbiri ya hypersensitivity ena thienopyridine, kuwunika kuyenera kuyang'aniridwa mosamala pakumwa kwa matenda a hypersensitivity to clopidogrel.

Matenda aimpso

Chithandizo cha Clopidogrel mwa odwala omwe ali ndi vuto laimpso ndilochepa. Chifukwa chake, pankhani ya odwala otere, mankhwalawa ayenera kugwiritsidwa ntchito mosamala.

Kuwonongeka kwa chiwindi

Zochitika kugwiritsa ntchito mankhwalawa odwala omwe ali ndi vuto la chiwindi, zolimbitsa thupi, zomwe zimapangitsa kuti hemorrhagic diathesis, ikhale yochepa. Pankhani imeneyi, mwa anthuwa, mankhwalawa ayenera kugwiritsidwa ntchito mosamala.

Mimba komanso kuyamwa

Chifukwa chosowa deta yakuchipatala pazotsatira za clopidogrel pa nthawi yomwe ali ndi pakati, ndikulangizidwa kuti musagwiritse ntchito clopidogrel pa nthawi ya pakati ngati chisamaliro.

Kafukufuku wammbuyo sanawonetse mavuto aliwonse mwachindunji kapena osakhudzana ndi mankhwalawa pathupi, kutukuka kwa embryonic / fetal, kubadwa kwa mwana kapena kubereka.

Sizikudziwika ngati clopidogrel imadutsa mkaka wa m'mawere a anthu. Kafukufuku wamtsogolo awonetsa kuti clopidogrel imadutsa mkaka wa m'mawere. Ngati chisamaliro, kuyamwitsa sikuyenera kupitilizidwa pakumwa mankhwalawa ndi clopidogrel-Teva.

Kafukufuku wamtsogolo sanawonetse kuti clopidogrel imakhudza chonde.

Zomwe zimachitika chifukwa cha mankhwalawa amatha kuyendetsa galimoto kapena njira zoopsa

Chifukwa chachilendo cha chizungulire kapena zovuta zina, mankhwalawa ayenera kugwiritsidwa ntchito mosamala mukamayendetsa ndi makina ogwiritsa ntchito.

ZOCHULUKITSA ZA ZAULERE

mankhwala. Clopidogrel amasankha mosamala kumangiriza kwa ADP ku mapulateleti othandizira ndi kutsegulira kwa glycoprotein (GP) IIb / IIIa zovuta ndipo motero kumalepheretsa kuphatikiza kwa mapulateleti. Clopidogrel imalepheretsanso kuphatikiza kwa mapulateleti chifukwa cha zinthu zina. Mankhwalawa sakhudza ntchito ya PDE.

Clopidogrel imasinthika mosasinthika mapulateleti a ADP, chifukwa chake mapulateleti amakhalabe osagwira ntchito moyo wonse, ndipo ntchito yabwinobwino imabwezeretseka pambuyo poti kukonzanso kwapulatelet (pafupifupi masiku 7 pambuyo pake). Chophatikizika chambiri komanso chodalirika cha kupanikizana kwa maplatifomu amadziwika patatha maola awiri atayamwa pakamwa limodzi la clopidogrel. Mobwerezabwereza makonzedwe a mlingo wa 75 mg kumayambitsa chopinga chachikulu cha kuphatikizidwa kwa maselo ambiri. Zotsatira zake zimakula pang'onopang'ono, ndipo khola limatha pambuyo pa masiku atatu. Komanso, avareji ya zoletsa kuphatikiza motsogozedwa ndi 75 mg ndi 40-60%. Kuphatikizana kwa magazi ndi magazi nthawi yobwerera kumayambira pakadutsa masiku 7 mutayimitsa clopidogrel.

Pharmacokinetics Mutatenga mlingo wa 75 mg, clopidogrel imatengedwa mwachangu m'mimba. Komabe, ndende yake m'magazi a m'magazi mulibe tanthauzo ndipo pambuyo pa maola 2 pambuyo pa chithandizo sikufikira muyeso (0.025 μg / l).

Clopidogrel imapangidwa mwachangu mu chiwindi. Metabolite yake yayikulu ndi yochokera mu carboxylic acid ndipo imakhala pafupifupi 85% ya zomwe zimangoyenda m'madzi a m'magazi. C_max wa metabolite mu madzi am`magazi pambuyo mobwerezabwereza Mlingo wa clopidogrel pa 75 mg ndi pafupifupi 3 mg / l ndipo zimatheka 1 ola pambuyo makonzedwe.

The pharmacokinetics of the metabolite yayikulu adawonetsa ubale wozungulira mkati mwa kuchuluka kwa Clopidogrel 50-150 mg. Clopidogrel ndi metabolite yake yayikulu imakanika kumapuloteni a plasma mu vitro (98 ndi 94%, motsatana). Chomangira ichi sichikhala chosapangidwa mu vitro pamitundu yambiri.

Mutatenga, pafupifupi 50% ya mankhwalawa amatengedwa mumkodzo ndipo pafupifupi 46% ndi ndowe mkati mwa maola 120 atatha kutsata. T_½ metabolite yayikulu ndi maola 8

Kuchuluka kwa metabolite yayikulu m'madzi a m'magazi kumakhala kwakukulu kwambiri mwa odwala okalamba (zaka 75) poyerekeza ndi odzipereka achinyamata achinyamata. Komabe, kuchuluka kwa plasma sikunayende limodzi ndi kusintha kwa kuphatikizika kwa maselo ndi nthawi yamagazi. Kuchulukitsidwa kwa metabolite yayikulu m'madzi am'magazi atatengedwa 75 mg / tsiku kumachepetsedwa kwambiri odwala omwe ali ndi vuto lalikulu la impso. ) komanso odzipereka athanzi.Ngakhale zovuta zoletsa kuphatikizira kwa mapulani a ADP-25 zimafupikitsidwa (25%) poyerekeza ndi odzipereka athanzi, nthawi yowukha magazi idatenga nthawi yofanana ndi odzipereka athanzi omwe amalandila clopidogrel pa mlingo wa 75 mg / tsiku.

kupewa mawonetseredwe a atherothrombosis akuluakulu:

• Odwala pambuyo myocardial infarction (chiyambi cha chithandizo - masiku angapo pambuyo pake, koma osadutsa masiku 35 kuchokera kumayambiriro kwake), ischemic stroke (chiyambi cha chithandizo - masiku 7, koma osapitirira miyezi 6 kuchokera kumayambiriro kwake) kapena wodwala matenda opatsirana mitsempha (kuwonongeka kwa mitsempha ndi atherothrombosis ya ziwiya zam'munsi),
• Odwala omwe ali ndi pachimake coronary syndrome (ACS):
• ndi ACS popanda kukweza gawo la S - T (kusakhazikika kwa angina pectoris kapena infaration ya myocardial yopanda Q wave), kuphatikiza pa odwala omwe adatsekeka nthawi yayitali mkati mwa coronary angioplasty, osakanikirana ndi acetylsalicylic acid,
• ndi pachimake myocardial infarction ndi kukwezeka kwa gawo la S - T, limodzi ndi acetylsalicylic acid (odwala omwe amalandila chithandizo chamankhwala omwe akuwonetsedwa chithandizo cha thrombolytic).

Kupewa kwa zochitika za atherothrombotic ndi thromboembolic ndi fibrillation ya atria: clopidogrel osakanikirana ndi acetylsalicylic acid akuwonetsedwa kwa odwala akuluakulu omwe ali ndi fibrillation ya atrial, omwe ali ndi vuto limodzi mwadzidzidzi chifukwa cha zochitika zamitsempha, zotsutsana ndi chithandizo cha magazi ndi antagonists amtsempha wamagazi. ndi zochitika zakale, kuphatikizapo stroke.

APPLICATION

Akuluakulu, kuphatikizapo odwala okalamba. Clopidogrel ndi mankhwala 75 mg 1 nthawi patsiku, ngakhale kudya.

Chithandizo cha Clopidogrel cha odwala omwe ali ndi ACS popanda kukweza gawo la S - T (gawo losakhazikika la angina pectoris kapena infarction ya Myocardial popanda Q wave pa ECG) imayamba ndi kutulutsa kamodzi kwa 300 mg, kenako ndikupitilira mlingo wa 75 mg kamodzi patsiku (ndi acetylsalicylic acid pa mlingo wa 75- 325 mg / tsiku). Popeza kugwiritsa ntchito milingo yapamwamba ya acetylsalicylic acid kumachulukitsa magazi, ndikulimbikitsidwa kuti musapitirire mlingo wa 100 mg. Kutalika kokwanira kwa chithandizo sikunakhazikitsidwe. Phindu logwiritsa ntchito mankhwalawa mpaka miyezi 12 idanenedwa, ndipo kuchuluka kwake kudachitika pambuyo pa miyezi itatu ya chithandizo.

Kwa odwala omwe ali ndi vuto lodana ndi kupweteka kwa mutu pachimake ndi kukwezeka kwa gawo la S - T, clopidogrel amalembedwa 75 mg kamodzi patsiku, kuyambira mlingo umodzi wa 300 mg osakanikirana ndi acetylsalicylic acid, wokhala ndi mankhwala osokoneza bongo kapena osapindika. Chithandizo cha odwala zaka zopitilira 75 zimayamba popanda kukweza mlingo wa clopidogrel. Kuphatikiza mankhwalawa kuyenera kuyambika posachedwa pambuyo pa kuyamba kwa zizindikiro ndikupitilira kwa milungu inayi. Ubwino wogwiritsa ntchito kuphatikizika kwa clopidogrel ndi acetylsalicylic acid kwa masabata opitilira 4 sunaphunzire matendawa.

Odwala omwe ali ndi fibrillation ya atrial, clopidogrel amagwiritsidwa ntchito limodzi mu 75 mg. Pamodzi ndi clopidogrel, kugwiritsa ntchito acetylsalicylic acid kuyenera kuyambitsidwa ndikupitilizidwa (pa mlingo wa 75-100 mg / tsiku).

Ngati mwasowa mlingo:

• Ngati maola osakwana 12 wadutsa kuchokera nthawi yomwe ayenera kumwa mlingo wotsatira, wodwalayo azitenga yomweyo mankhwalawo, ndipo mlingo wotsatira uyenera kumwedwa nthawi yomweyo.
• Ngati maola opitilira 12 adatha, wodwalayo atengere mlingo wotsatira nthawi yotsatira, koma osachulukitsa kawiri mlingo kuti mulipire mlingo womwe mwasowa.

Kulephera kwina. Zowonjezera zothandizira kugwiritsa ntchito mankhwalawa kwa odwala omwe ali ndi vuto la impso ndizochepa.

Kulephera kwa chiwindi. Zowonjezera zochizira kugwiritsa ntchito mankhwalawa odwala omwe ali ndi matenda olimba a chiwindi komanso chiopsezo cha hemorrhagic diathesis ndizochepa.

ZOCHITITSA ZONSE

magazi amatchulidwa kuti ndiwosangalatsa ndipo nthawi zambiri amapezeka mwezi woyamba wa chithandizo.

Zotsatira zoyipa zimagawidwa pakati pa ziwalo, pafupipafupi momwe zimakhalidwira zimafotokozedwa motere: nthawi zambiri (kuyambira ≥1 / 100 mpaka ≤1 / 10), kawirikawiri (kuyambira ≥1 / 1000 mpaka ≤1 / 100), kawirikawiri (kuyambira ≥1 / 10,000 mpaka ≤ 1/1000), kawirikawiri (kuchokera kozungulira ndi pamitsempha yamagetsi: kawirikawiri - thrombocytopenia, leukopenia, eosinophilia, neutropenia, kuphatikizapo kwambiri neutropenia, kawirikawiri - thrombotic thrombocytopenic purpura, aplasic anemia, pancytopenia, agranulocytosis, .

Pa gawo la chitetezo chamthupi: kawirikawiri - seramu matenda, anaphylactoid zimachitika, osadziwika - mtanda-hypersensitivity pakati thienopyridine (monga ticlopidine, prasugrel) (onani MALANGIZO OTHANDIZA).

Kuchokera ku psyche: kawirikawiri - kuyerekezera, kusokoneza.

Kuchokera ku dongosolo lamanjenje: kawirikawiri - magazi a intracranial (nthawi zina, amafa), kupweteka kwa mutu, paresthesia, chizungulire, kawirikawiri - kusintha kwa kukoma.

Kuchokera kumbali ya chiwalo cha masomphenyawo: pafupipafupi - magazi m'dera lamaso (conjunctival, ocular, retinal).

Pa gawo la kumva: osowa - chizungulire.

Kuchokera ku ziwiya: nthawi zambiri - hematoma, kawirikawiri - kukha magazi kwakukulu, magazi kuchokera ku bala la opaleshoni, vasculitis, ochepa hypotension.

Kuchokera kupuma dongosolo: Nthawi zambiri - nosebleeds, kawirikawiri - magazi kupuma thirakiti (hemoptysis, pulmonary hemorrhage), bronchospasm, pneumonitis, eneinonilic.

Kuchokera pamimba yodyetsera: pafupipafupi - kutaya magazi m'mimba, kutsekula m'mimba, kupweteka kwam'mimba, dyspepsia, pafupipafupi - zilonda zam'mimba, zilonda zam'mimba, gastritis, kusanza, nseru, kudzimbidwa, kuchepa kwamitsempha, kawirikawiri - kuchepa kwa magazi m'mimba, kawirikawiri - m'mimba kupweteka kwa kuchepa kwa mitsempha yotupa, kapamba, khansa (makamaka zilonda zam'mimba kapena zam'mimba), stomatitis.

Kuchokera ku hepatobiliary system: kawirikawiri kwambiri - kulephera kwa chiwindi, chiwindi, zotsatira zoyipa zamayendedwe a chiwindi.

Pa khungu ndi subcutaneous minofu: pafupipafupi - subcutaneous kukha magazi, kawirikawiri - zidzolo, kuyabwa, intradermal hemorrhage (purpura), kawirikawiri - bulous dermatitis (erythema multiforme), angioedema, cutaneous kapena exfoliane , urticaria, hypersensitivity syndrome, mankhwala osokoneza bongo omwe amakhala ndi eosinophilia komanso mawonekedwe a systemic (DRESS syndrome), eczema, lichen planus.

Kuchokera ku minculoskeletal system: kawirikawiri - musculoskeletal hemorrhage (hemarthrosis), nyamakazi, arthralgia, myalgia.

Kuchokera impso ndi kwamikodzo dongosolo: pafupipafupi - hematuria, osowa - glomerulonephritis, kuchuluka kwa creatinine m'magazi.

Zomwe zimachitika pakapita jakisoni: nthawi zambiri - magazi m'malo a jakisoni, kawirikawiri - malungo.

Maphunziro a labotale: kawirikawiri - nthawi yayitali yotaya magazi, kuchepa kwa chiwerengero cha neutrophils ndi mapulateleti.

MALANGIZO OTHANDIZA

magazi ndi matenda a m'matumbo ogwirizana ndi zovuta za hematological. Ngati zizindikiro za kutuluka magazi zadziwika panthawi yogwiritsa ntchito mankhwalawa, kuyezetsa magazi mwatsatanetsatane ndi / kapena kuyesedwa koyenera kuyenera kuchitidwa nthawi yomweyo. Monga othandizirana ndi ma antiplatelet othandizira, clopidogrel iyenera kugwiritsidwa ntchito mosamala kwa odwala omwe ali ndi chiopsezo chowonjezereka cha magazi chifukwa cha kuvulala, opareshoni kapena zochitika zina zamatenda, komanso pankhani ya odwala omwe amagwiritsa ntchito acetylsalicylic acid, heparin, IIb / IIIa glycoprotein inhibitors kapena NSAIDs, makamaka COX-inhibitors 2 kapena kusankha serotonin reuptake inhibitors (SSRIs). Ndikofunikira kuyang'anira mosamala mawonetseredwe am'magazi owonekera m'magazi, kuphatikiza magazi obisika, makamaka masabata oyamba a chithandizo komanso / kapena pambuyo panjira yolowerera pamtima ndi kuchitapo kanthu.Kugwiritsa ntchito nthawi imodzimodziyo kwa clopidogrel ndi anticoagulants sikulimbikitsidwa, popeza izi zitha kuwonjezera kuchuluka kwa magazi.

Pankhani ya opaleshoni yomwe mwakonzekera kuti pakanthawi panu sipafunike mankhwala ogwiritsira ntchito antiplatelet, mankhwalawa ndi clopidogrel ayenera kusiyidwa masiku 7 asanachitike opaleshoni. Odwala ayenera kudziwitsa madokotala, kuphatikizapo akatswiri a mano, kuti akumwa clopidogrel, opaleshoni iliyonse isanafike, kapena musanayambe kugwiritsa ntchito mankhwala atsopano. Clopidogrel imachulukitsa kutalika kwa magazi, choncho iyenera kugwiritsidwa ntchito mosamala mu odwala omwe ali ndi chiopsezo chotaya magazi (makamaka m'mimba komanso intraocular).

Odwala ayenera kuchenjezedwa kuti pochiza matenda a clopidogrel (yekha kapena osakanikirana ndi acetylsalicylic acid), magazi amatha kusiya pambuyo pake, ndikuti adziwitse dokotalayo za vuto lililonse losatulutsa magazi (m'malo kapena nthawi).

Supombotic thrombocytopenic purpura. Milandu ya thrombotic thrombocytopenic purpura (TTP) sakhala ikupezeka kawirikawiri kwambiri atagwiritsidwa ntchito ndi clopidogrel, nthawi zina ngakhale atagwiritsidwa ntchito kwakanthawi kochepa. TTP imawonetsedwa ndi thrombocytopenia ndi microangiopathic hemolytic anemia yodziwonetsa minyewa, kukanika kwa aimpso, kapena kutentha thupi. TTP ikhoza kukhala vuto lomwe lingathe kupha, chifukwa chake limafunikira chithandizo cham'tsogolo, kuphatikizapo plasmapheresis.

Anapeza hemophilia. Kupanga kwa hemophilia atagwiritsidwa ntchito clopidogrel kwatchulidwa. Potsimikizira kuchuluka kwa nthawi yokhazikitsidwa ndi gawo la thromboplastin nthawi (APTT) kapena popanda magazi, makulidwe a hemophilia omwe akuyembekezeredwa ayenera kuganiziridwa. Odwala otere ayenera kusiya kugwiritsa ntchito clopidogrel ndi kukaonana ndi katswiri kuti apeze chithandizo choyenera.

Posachedwa wavutika ischemic stroke. Chifukwa chosakwanira, sizikulimbikitsidwa kuti mupereke mankhwala a clopidogrel m'masiku 7 oyamba atatha kupweteka kwa ischemic.

Cytochrome P450 2C19 (CYP 2C19). Mankhwala. Odwala ndi chibadwa yafupika ntchito CYP 2C19, m'munsi ndende ya yogwira metabolop ya magazi mu plasma ndi zochepa kutchulidwa antiplatelet zotsatira zimadziwika. Pali mayeso omwe amatha kudziwa mtundu wa CYP 2C19 genotype wodwala.

Popeza clopidogrel imasinthidwa kukhala yogwira metabolite pang'ono pazochitika za CYP 2C19, kugwiritsa ntchito mankhwala omwe amachepetsa ntchito ya enzymeyi kungayambitse kuchepa kwa kuchuluka kwa metabolite ya clopidogrel m'magazi a m'magazi. Komabe, kufunikira kwakukhudzaku mukulumikizanaku sikunafotokozeredwe. Chifukwa chake, ngati njira yodzitetezera, kugwiritsa ntchito mitundu inanso ya CYP 2C19 molimba komanso moyenera kuyenera kupewedwa (onani ZINSINSI).

Thupi lama-allergic. Odwala ayenera kufufuzidwa kuti awone mbiri ya hypersensitivity kwa thienopyridine ena (monga ticlopidine, prasugrel), popeza pakhala pali malipoti okhudza kuyanjana pakati pa thienopyridines (onani ZOTHANDIZA ZAKUTI).

Thienopyridines angayambitse zolimbitsa kwambiri thupi lawo siligwirizana, monga angioedema, zidzolo, hematological mtanda zimachitika (thrombocytopenia, neutropenia).

Odwala omwe ali ndi mziwopsezo komanso / kapena ma hematologic akamagwiritsira ntchito mankhwala ochokera ku gulu la thienopyridine akhoza kukhala ndi chiopsezo chowonjezereka chomwenso mumagwiritsa ntchito thienopyridine ena. Chifukwa chake, odwala otere ayenera kuyang'aniridwa bwino.

Magulu apadera a odwala. Zochizira ndi clopidogrel mwa odwala omwe amalephera kupweteka kwa impso ndizochepa, chifukwa chake, odwala oterewa amayenera kupatsidwa mankhwala mosamala (onani.APPLICATION).

Zomwe mungagwiritse ntchito mankhwalawa kwa odwala omwe ali ndi matenda a chiwindi komanso kuchuluka kwa hemorrhagic diathesis ndizochepa. Chifukwa chake, clopidogrel iyenera kutumizidwa kwa odwala mosamala (onani APPLICATION).

Othandizira. Clopidogrel-Teva muli lactose. Odwala omwe ali ndi matenda osowa kwambiri monga galactose tsankho, kuperewera kwa lappase kapena kufupika kwa glucose-galactose malabsorption sayenera kumwa mankhwalawa.

Njira zopewera kutaya zinyalala. Zotsalira kapena mankhwala zinyalala osagwiritsidwa ntchito ziyenera kutayidwa malinga ndi malamulo akwawoko.

Gwiritsani ntchito panthawi yoyembekezera komanso mkaka wa m`mawere. Chifukwa cha kusowa kwa zachipatala, kugwiritsidwa ntchito kwa clopidogrel panthawi yoyembekezera ndikosayenera kwa amayi apakati (mosamala).

Kafukufuku wazinyama sanawonetse vuto lakumodzi kapena losawonekera pakubala, mwana wosabadwayo / kakulidwe ka mwana, kubala kwa mwana ndi kubereka.

Sizikudziwika ngati ma clopidogrel adachotsedwa mkaka wa m'mawere. Kafukufuku wazinyama adawonetsa kuti clopidogrel imadutsa mkaka wa m'mawere, chifukwa chake, kuyamwitsa kuyenera kuyimitsidwa pakumwa mankhwalawa ndi clopidogrel.

Chonde. Kafukufuku wazinyama zothandizira ntchito sanawonetse zoyipa za clopidogrel pachonde.

Ana. Clopidogrel-Teva sanalembedwe kwa ana.

Kutha kukopa momwe zinthu zikuyendera mukamayendetsa magalimoto kapena njila zina. Clopidogrel siyimakhudza kapena imakhala yovuta pang'ono pakutha kuyendetsa magalimoto kapena njila zina.

ZINSINSI

anticoagulants pamlomo. Kugwiritsa ntchito nthawi yomweyo clopidogrel ndi anticoagulants sikulimbikitsidwa, popeza kuphatikiza kotereku kumapangitsa kuchuluka kwa magazi. Ngakhale kugwiritsidwa ntchito kwa clopidogrel pa mlingo wa 75 mg / tsiku sikusintha mbiri ya pharmacokinetic ya S-warfarin kapena chiwembu chofananira padziko lonse lapansi (INR) mwa odwala omwe amathandizidwa ndi warfarin kwa nthawi yayitali, kugwiritsa ntchito nthawi yomweyo kwa clopidogrel ndi warfarin kumawonjezera mwayi wamagazi chifukwa chodziyimira pawokha zotsatira za heestasis.

Glycoprotein IIb / IIIa zoletsa. Clopidogrel iyenera kugwiritsidwa ntchito mosamala kwa odwala omwe ali ndi chiopsezo chowonjezereka cha magazi chifukwa chatsoka, opaleshoni kapena zochitika zina zam'magazi momwe IIb / IIIa glycoprotein receptor inhibitors amagwiritsidwa ntchito munthawi yomweyo.

Acetylsalicylic acid. Acetylsalicylic acid sasintha choletsa kuchuluka kwa clopidogrel pa ADP-anachititsa kupatsidwa zinthu za m'magazi, koma Clopidogrel imawonjezera zotsatira za acetylsalicylic acid pamaphatikizidwe ophatikizidwa ndi collagen. Komabe, kugwiritsa ntchito munthawi yomweyo 500 mg ya acetylsalicylic acid 2 pa tsiku kwa tsiku limodzi, sikunayambitse kuchuluka kwa magazi nthawi yayitali, yayitali chifukwa cha clopidogrel. Popeza kuphatikiza kwa pharmacodynamic pakati pa clopidogrel ndi acetylsalicylic acid ndikotheka ndikuwonjezera magazi, munthawi yomweyo kugwiritsa ntchito mankhwalawa kumafunikira kusamala. Ngakhale zili choncho, pali zinachitikira kutenga clopidogrel ndi acetylsalicylic acid limodzi mpaka chaka chimodzi.

Heparin. Zinanenedwa kuti clopidogrel sifunikira kusintha kwa heparin ndipo sikukhudza mphamvu ya heparin pakuwundana. Kugwiritsa ntchito nthawi imodzi kwa heparin sikunasinthe kufooka kwa mphamvu ya Clopidogrel pa kuphatikizidwa kwa maselo ambiri. Popeza kulumikizana kwa pharmacodynamic pakati pa clopidogrel ndi heparin ndikotheka ndikuwonjezereka kwa magazi, munthawi yomweyo kugwiritsa ntchito mankhwalawa kumafunikira kusamala.

Othandizira a thrombolytic.Kutetezedwa kwa munthawi yomweyo kugwiritsa ntchito clopidogrel, fibrin-eni kapena fibrin-enieni a thrombolytic othandizira ndi heparin anaphunziridwa mwa odwala omwe ali ndi infarate ya myocardial. Pafupipafupi magazi akuwonekera kwambiri anali ofanana ndi omwe amapezeka ndi munthawi yomweyo mankhwala osokoneza bongo a hepatin ndi heparin wokhala ndi acetylsalicylic acid.

NSAIDs. Kugwiritsidwa ntchito kwina kwa clopidogrel ndi naproxen akuti kukuwonjezera kuchuluka kwa magazi am'mimba omwe amatuluka. Komabe, chifukwa cha kuchepa kwa maphunziro pakukhudzana ndi mankhwalawo ndi ena a NSAID, sizinadziwikebe kuti kaya chiwopsezo cha kutaya magazi m'mimba chimagwiritsidwa ntchito bwanji ndi ma NSAID onse. Chifukwa chake, kusamala ndikofunikira mukamagwiritsa ntchito NSAIDs, makamaka COX-2 inhibitors, yokhala ndi clopidogrel.

Kusankha Serotonin Reuptake Inhibitors (SSRIs). Popeza kuti ma SSRIs amakhudza kutsegula kwa magazi a m'magazi ndi kuwonjezera ngozi ya magazi, kugwiritsa ntchito nthawi yomweyo kwa SSRIs ndi clopidogrel kumafuna kusamala.

Kuphatikiza ndi mankhwala ena. Popeza clopidogrel imasinthidwa kukhala yogwira metabolite pang'ono pazochitika za CYP 2C19, kugwiritsa ntchito mankhwala omwe amachepetsa ntchito ya enzymeyi kungayambitse kuchepa kwa kuchuluka kwa metabolite ya clopidogrel m'magazi a m'magazi. Kufunika kwachipatala pakuyanjanaku sikunafotokozeredwe. Chifukwa chake, ngati njira yodzitetezera, kugwiritsa ntchito nthawi imodzi yamphamvu komanso yolimbitsa CYP 2C19 kuyenera kupewedwa.

Mankhwala omwe amalepheretsa ntchito ya CYP 2C19 akuphatikiza omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxacarbazepine ndi chloramphenicol.

Proton pump zoletsa. The kuchuluka kwa yogwira metabolite m'magazi anachepa ndi munthawi yomweyo kugwiritsa ntchito kapena maola 12 pakati Mlingo wa clopidogrel ndi omeprazole pa mlingo wa 80 mg. Kuchepetsa uku kumatsatiridwa ndi kuchepa kwa kuponderezana kwa kuphatikizana kwa maplatelet. Esomeprazole akuyembekezeka kulowa mgulu lofanananso ndi clopidogrel.

Kuchepa kocheperachepera mu ndende ya metabolite m'magazi kunadziwika ndi pantoprazole kapena lansoprazole.

Zachuma kwambiri cha pharmacodynamic mogwirizana ndi kugwiritsa ntchito Clopidogrel munthawi yomweyo ndi atenolol, nifedipine, kapena ndi mankhwala onsewa sizinadziwikebe. Kuphatikiza apo, pharmacodynamic ntchito ya clopidogrel idasinthiratu osagwiritsa ntchito phenobarbital ndi estrogen.

Zotsatira za digoxin kapena theophylline sizinasinthe pogwiritsa ntchito clopidogrel.

Maantacidid sichinakhudze mulingo woyamwa wa clopidogrel.

Mphamvu ya antithrombotic zochita za clopidogrel imatha kuchepetsedwa ndi theka pomwe ikuphatikizidwa ndi proton pump inhibitors. Pankhaniyi, kusiyana kwa kayendetsedwe ka nthawi sikukhudza kuchepa kwa mphamvu ya clopidogrel. Kuphatikizidwa kwa clopidogrel ndi proton pump inhibitors sikulimbikitsidwa.

Carboxylic clopidogrel metabolites imatha kuletsa ntchito ya cytochrome P450 2C9. Izi zitha kukulitsa kuchuluka kwa mankhwala a plasma monga phenytoin ndi tolbutamide, ndi ena omwe amapangidwa pogwiritsa ntchito cytochrome P450 2C9. Ngakhale izi, zotsatira za kafukufuku wazachipatala zimawonetsa kuti phenytoin ndi tolbutamide zitha kugwiritsidwa ntchito mosamala ndi clopidogrel.

Kupatula pachidziwitso cha kuyanjana ndi mankhwala enieni omwe tapatsidwa pamwambapa, maphunziro pazokhudzana ndi clopidogrel ndi mankhwala omwe nthawi zambiri amaperekedwa kwa odwala omwe ali ndi atherothrombosis sanachitike.Komabe, odwala omwe adatenga nawo gawo pazachipatala zama Clopidogrel adagwiritsa ntchito mankhwala ena nthawi yomweyo, kuphatikizapo okodzetsa, β-adrenoreceptor blockers, ma inhibitors a ACE, othandizira othandizira calcium, othandizira a cholesterol, othandizira ma antiodilentic, mankhwala opatsirana mankhwala ndi othandizira a GPIIb / IIIa, popanda umboni wazovuta zoyipa.

CHONCHO

Ndi bongo wa clopidogrel, kuwonjezeka kwa nthawi yamagazi ndi zovuta zina zamtsogolo ndizotheka. Pankhani ya magazi, chithandizo chamankhwala chimalimbikitsidwa.

Clididogrel antidote sichikudziwika. Ngati kukonzanso mwachangu kwa nthawi yayitali pakukha magazi ndikofunikira, mphamvu ya clopidogrel imatha kuyimitsidwa ndikuthiratu kupatsidwa magazi.

Malangizo ogwiritsira ntchito clopidogrel-teva

Mapiritsi - 1 piritsi:

Zinthu zogwira: clopidogrel - 75 mg,

7 kapena 10 ma PC. - matuza (2, 4, 8, 9, 12) - mapaketi a makatoni.

Pambuyo pakamwa pakamwa pa 75 mg, clopidogrel imatengedwa mwachangu kuchokera m'mimba. Komabe, kuchuluka kwa plasma yamagazi kumachulukako pang'ono ndipo pambuyo pa maola 2 pambuyo pa utsi sikufika pamlingo womwe ungatsimikizidwe (0.025 μg / L).

Mothandizidwa kwambiri mu chiwindi. Metabolite yayikulu imachokera ku carboxylic acid ndipo imapanga 85% yazinthu zoyambira kuzungulira plasma. Cmax ya metabolite iyi m'madzi a m'magazi pambuyo pobwereza Mlingo wa clopidogrel ndi pafupifupi 3 mg / l ndipo amawonedwa pafupifupi ola limodzi pambuyo pa kuperekedwa.

The pharmacokinetics ya metabolite yayikulu imadziwika ndi mzere wothandizirana muyezo wa clopidogrel 50-150 mg.

Clopidogrel ndi metabolite wamkulu sangathe kusintha mapuloteni a plasma mu vitro (98% ndi 94%, motsatana). Chiyanjano ichi sichikhala chosapangidwa mu vitro pazowunika zosiyanasiyana.

Pambuyo pakuyamwa kwa 14C-cholembedwa clopidogrel, pafupifupi 50% ya mankhwalawa amatengedwa mumkodzo ndipo pafupifupi 46% ndi ndowe kwa maola 120. T1 / 2 ya metabolite yayikulu ndi maola 8.

Poyerekeza ndi odzipereka achinyamata athanzi, kuchuluka kwa plasma kwa metabolite yayikulu kumakhala kwakukulu kwambiri mwa odwala okalamba (azaka 75 ndi akulu), popanda kusintha kwa kuphatikizana kwa maselo a magazi ndi nthawi ya magazi.

M'matenda akulu a impso (CC 5-15 ml / min), kuchuluka kwa metabolite yayikulu m'madzi am'madzi kumakhala kocheperako poyerekezera ndi matenda a impso (CC 30-60 ml / min) komanso odzipereka athanzi. Ngakhale zovuta zoletsa kuphatikizira kwa mapulani am'magazi a ADP zidachepetsedwa poyerekeza ndi za odzipereka athanzi, nthawi yowukha magazi idakulirakulira chimodzimodzi ndi ya odzipereka athanzi.

Pulatelet Aggregation Inhibitor. Mosamala amalepheretsa kumangiriza kwa adenosine diphosphate (ADP) kwa mapulateleti othandizira ndi kutsegulira kwa GPIIb / IIIa tata, motero kuletsa kuphatikizidwa kwa ma cell. Imalepheretsanso kuphatikiza kwa maselo am'magazi oyambitsidwa ndi agonists ena poletsa kuchuluka kwa mapulateleti ndi AdP yotulutsidwa. Sizikhudza zochita za PDE.

Clopidogrel sasintha mosasinthika ma receptors a ADP pamapulateleti, kotero mapulateleti amakhalabe osagwira ntchito mu "moyo" wawo wonse, ndipo ntchito yabwinobwino imabwezeretsedwa pamene ikukonzedwanso (pambuyo masiku pafupifupi 7).

Zisonyezero zogwiritsa ntchito clopidogrel-teva

Kupewera kwa zovuta za thrombotic kwa odwala omwe ali ndi myocardial infarction, ischemic stroke, kapena paripheral artery occlusion. Kuphatikiza ndi acetylsalicylic acid woletsa masokonezo am'matumbo am'mimba kwambiri: ndi kukwera kwa ST ndi gawo la chithandizo cha thrombolytic, popanda ST gawo kukweza (kusakhazikika kwa angina pectoris, infarction ya myocardial yopanda Q wave)odwala akudwala.

Kupewera kwa zovuta za thrombotic ndi thromboembolic, kuphatikizapo stroke, ndi atrive fibrillation (atental fibrillation) pamaso pa chinthu chimodzi chokha chothandizira kukulitsa kwamisempha, kulephera kutenga anticoagulants osadziwika ndi chiopsezo chochepa cha magazi (kuphatikiza ndi acetylsalicylic acid).

Ntchito Clopidogrel-teva pakati ndi ana

Maphunziro okwanira komanso osamalidwa mosamalitsa a chitetezo cha clopidogrel panthawi yoyembekezera sanachitike. Kugwiritsa ntchito kumatheka pokhapokha mwadzidzidzi.

Sizikudziwika ngati ma clopidogrel omwe ali ndi mkaka wa m'mawere amawachotsa mwa anthu. Ngati ndi kotheka, ntchito pa mkaka wa m`mawere ayenera kusankha pa kuyamwitsa.

Mu kafukufuku wazinyama woyeserera pogwiritsa ntchito clopidogrel mu Mlingo wa 300-500 mg / kg / tsiku, palibe zotsatira za teratogenic komanso zoyipa zomwe zimachitika pakubala komanso fetal zimapezeka. Zinakhazikitsidwa kuti clopidogrel ndi ma metabolites ake amachotseredwa mkaka wa m'mawere.

Mlingo wa Clopidogrel Teva

Tengani pakamwa nthawi 1 / tsiku.

Mlingo woyambirira komanso wokonza ndi 75 mg / tsiku. Mulingo wokweza ndi 300 mg / tsiku.

Ma regimen ogwiritsira ntchito amatengera zomwe zikuwonetsa ndi zomwe zikuchitika.

Clopidogrel amagwiritsidwa ntchito mosamala ndi chiwopsezo chowonjezereka cha kutaya magazi chifukwa cha kuvulala, kuchitapo kanthu kwa opaleshoni, komanso kusokonezeka kwa dongosolo la heestasis. Ndi chithandizo chopangira opaleshoni (ngati antiplatelet athari ndi chosafunikira), clopidogrel iyenera kuyimitsidwa masiku 7 asanachitike opaleshoni.

Clopidogrel amagwiritsidwa ntchito mosamala odwala omwe ali ndi vuto la chiwindi, komwe hemorrhagic diathesis imatha kuchitika.

Zizindikiro zakutulutsa magazi kwambiri (m'kamwa, magazi m'matumbo am'mimba, hematuria), kuwunika kwa hemostatic system (nthawi ya kukhetsa magazi, kuwerengetsa kupatsidwa zinthu za m'magazi, ziwonetsero zamagulu ena ogwira ntchito) zimasonyezedwa. Kuwunikira pafupipafupi kwa zizindikiro zamankhwala zolimbitsa thupi za chiwindi kumalimbikitsidwa.

Gwiritsani ntchito mosamala nthawi yomweyo ndi warfarin, heparin, NSAIDs, kwa nthawi yayitali - ndi acetylsalicylic acid, chifukwa Pakadali pano, chitetezo chamtunduwu sichinakhazikike.

M'maphunziro oyesera, palibe zotsatira zamafuta ndi genotoxic zomwe zidapezeka.

Kukopa pa kuyendetsa magalimoto ndi kayendedwe kazinthu

Mavuto a Clopidogrel pakutha kuyendetsa magalimoto ndi kayendedwe kazinthu sikunakhazikitsidwe.

Bongo

Ndi bongo wa clopidogrel, kuwonjezeka kwa magazi nthawi yotsatira ndi zovuta zina zitha kuwonedwa. Pankhani ya magazi, chithandizo chamankhwala chimalimbikitsidwa.

Katundu wa zochita za clopidogrel sakudziwika. Ngati mukufunikira kusintha nthawi yochulukitsa magazi nthawi, mphamvu ya clopidogrel imatha kuimitsidwa ndikuwonjezera magazi.

Gwiritsani ntchito pa nthawi yoyembekezera kapena mkaka wa m'mawere

Chifukwa chosowa deta yakuchipatala pakugwiritsa ntchito clopidogrel pa nthawi yapakati, ndikosaloledwa kupereka kwa amayi apakati (mosamala).

Kafukufuku wazinyama sanawonetse vuto lakumodzi kapena losawonekera pakubala, mwana wosabadwayo / kakulidwe ka mwana, kubala kwa mwana ndi kubereka.

Sizikudziwika ngati clopidogrel adachotsedwa mkaka wa m'mawere. Kafukufuku wazinyama adawonetsa kuti clopidogrel imachotsedwa mkaka wa m'mawere, kotero kuyamwitsa kuyenera kusiyidwa pakumwa mankhwala a clopidogrel.

Kafukufuku wazinyama zothandizira ntchito sanawonetse zoyipa za clopidogrel pachonde.

Clopidogrel-Teva sanalembedwe kwa ana.

Zolemba ntchito

Kupuma komanso matenda a m'magazi omwe amakhudzana ndi zovuta za hematological.

Ngati mukugwiritsa ntchito mankhwalawa pali zizindikiro zosonyeza kuti mungataye magazi, kuyezetsa magazi kwakukulu ndi / kapena kuyesedwa koyenera kuyenera kuchitidwa nthawi yomweyo. Monga othandizira ena a antiplatelet, clopidogrel iyenera kugwiritsidwa ntchito mosamala kwa odwala omwe ali ndi chiopsezo chowonjezereka cha magazi chifukwa cha kuvulala, opareshoni kapena zina zodwala, komanso mwa odwala omwe amagwiritsa ntchito ASA, heparin, IIb / IIa glycoprotein inhibitors kapena mankhwala osagwiritsa ntchito mankhwala a anti-yotupa, makamaka COX-inhibitors 2 kapena kusankha mankhwala a serotonin reuptake inhibitors (SSRIs) kapena mankhwala ena omwe angakulitse chiopsezo chotulutsa magazi (i.e. pentox asillin). Ndikofunikira kuyang'anira mosamala mawonetseredwe am'magazi owonetsa magazi m'magazi, kuphatikiza magazi obisika, makamaka masabata oyamba a chithandizo komanso / kapena pambuyo panjira yolowerera pamtima ndi kuchitapo kanthu. Kugwiritsa ntchito pamodzi nthawi yomweyo kwa clopidogrel ndi anticoagulants sikulimbikitsidwa, chifukwa kumatha kuwonjezera kuchuluka kwa magazi.

Pofuna kuchitidwa opaleshoni yomwe yakonzedwa, pakanthawi kochepa pamafunika kugwiritsa ntchito ma antiplatelet othandizira, mankhwalawa ndi clopidogrel ayenera kusiyidwa masiku 7 asanachitike opaleshoni. Odwala ayenera kufotokozera madokotala, kuphatikiza madokotala a mano kuti akuwamwa clopidogrel, musanawafotokozere opareshoni iliyonse kapena musanagwiritse ntchito mankhwala atsopano. Clopidogrel imachulukitsa kutalika kwa magazi, choncho iyenera kugwiritsidwa ntchito mosamala odwala omwe ali ndi chiopsezo chotaya magazi (makamaka m'mimba ndi intraocular).

Odwala ayenera kuchenjezedwa kuti pakumwa mankhwalawa ndi clopidogrel (yekha kapena osakanikirana ndi ASA), kutuluka magazi kumatha kutha kuposa masiku onse, ndikuti adziwitse dokotalayo za vuto lililonse losatulutsa magazi (m'malo mwake kapena nthawi yayitali).

Thrombotic thrombocytopenic purpura (TTP).

Milandu ya thrombotic thrombocytopenic purpura (TTP) siinawoneke kwambiri kawirikawiri pambuyo pa kayendetsedwe ka clopidogrel, nthawi zina ngakhale atagwiritsidwa ntchito kwakanthawi kochepa. TTP imawonetsedwa ndi thrombocytopenia ndi microangiopathic hemolytic anemia yodziwonetsa minyewa, kukanika kwa aimpso, kapena kutentha thupi. TTP ikhoza kukhala mkhalidwe womwe ungaphetse chifukwa chake imafunikira chithandizo cham'tsogolo, kuphatikizapo plasmapheresis.

Kupanga kwa hemophilia atagwiritsidwa ntchito clopidogrel kwatchulidwa. Potsimikizira kuchuluka kwa nthawi yokhazikitsidwa ndi gawo la thromboplastin nthawi (APTT) kapena popanda magazi, makulidwe a hemophilia omwe akuyembekezeredwa ayenera kuganiziridwa. Odwala otere ayenera kusiya kugwiritsa ntchito clopidogrel ndi kukaonana ndi katswiri kuti apeze chithandizo choyenera.

Posachedwa wavutika ischemic stroke.

Chifukwa chosakwanira, sizikulimbikitsidwa kuti mupereke mankhwala a clopidogrel m'masiku 7 oyamba atatha kupweteka kwa ischemic.

Cytochrome P450 2C19 (CYP2C19).

Mankhwala. Odwala ndi chibadwa yafupika ntchito CYP2C19, m'munsi ndende ya yogwira metabolop ya clopidogrel mu plasma ndi zochepa kutchulidwa antiplatelet zotsatira. Pali mayeso oti adziwe mtundu wa CYP2C19 genotype.

Popeza clopidogrel imatembenuzidwa kukhala yogwira metabolite pang'ono pazochitika za CYP2C19, kugwiritsa ntchito mankhwala omwe amachepetsa ntchito ya enzymeyi kungayambitse kuchepa kwa kuchuluka kwa metabolite ya clopidogrel mu plasma. Komabe, kufunikira kwakukhudzaku mukulumikizanaku sikunafotokozeredwe. Chifukwa chake, ngati njira yoteteza, kugwiritsa ntchito ma inhibitors a CYP2C19 molimba komanso moyenera ayenera kupewedwa (onani.Gawo "Kuyanjana ndi mankhwala ena ndi mitundu ina yoyanjana").

Clopidogrel iyenera kugwiritsidwa ntchito mosamala odwala omwe nthawi yomweyo amatenga zinthu zomwe zimakhala gawo la CYP2C8 cytochrome.

Thupi lama-allergic.

Odwala ayenera kufufuzidwa kuti awone mbiri ya hypersensitivity kwa ena thienopyridine (monga ticlopidine, prasugrel), popeza pakhala pali malipoti okhudza kuyanjana pakati pa thienopyridines (onani gawo "Zotsatira zosasinthika").

Thienopyridines angayambitse zolimbitsa kwambiri thupi lawo siligwirizana, monga angioedema, zidzolo, hematological mtanda zimachitika (thrombocytopenia, neutropenia).

Odwala omwe adakhalapo ndi mbiri yokhudzana ndi matupi awo sagwirizana komanso / kapena masinthidwe a hematological akamagwiritsa ntchito mankhwala ochokera ku gulu la thienopyridine akhoza kukhala ndi chiopsezo chowonjezereka chomwenso mumagwiritsa ntchito thienopyridine. Chifukwa chake, kwa odwala otere ayenera kuyang'aniridwa mosamala.

Magulu apadera a odwala.

Zochitika zochizira ndi clopidogrel odwala omwe ali nawo kulephera kwa aimpso Ochepa, motero, odwala otere ayenera kuyamwa mankhwalawa mosamala (onani Gawo "Mlingo ndi Ulamuliro").

Zochitika kugwiritsa ntchito mankhwalawa odwala matenda a chiwindi zolimbitsa thupi komanso kuthekera kwa hemorrhagic diathesis ndizochepa. Chifukwa chake, clopidogrel iyenera kutumizidwa kwa odwala mosamala (onani Gawo "Mlingo ndi Ulamuliro").

Clopidogrel-Teva muli lactose. Odwala omwe ali ndi matenda osowa monga chibadwa cha galactose, kuperewera kwa lappase kapena kufupika kwa glucose-galactose malabsorption sayenera kumwa mankhwalawa.

Njira zopewera kusamala potaya zinyalala

Zotsalira kapena mankhwala zinyalala osagwiritsidwa ntchito ziyenera kutayidwa malinga ndi malamulo apafupi.

Kuyanjana ndi mankhwala ena ndi mitundu ina yoyanjana

Mankhwala omwe angapangitse kuti magazi atuluke

Pali chiwopsezo chowonjezereka cha kutaya magazi chifukwa chakuwopsa kwa zotsatira za mankhwala. Gwiritsani ntchito mosamala mankhwala ena omwe angakulitse mwayi wokhetsa magazi.

Ma anticoagulants amlomo. Kugwiritsa ntchito nthawi yomweyo clopidogrel ndi anticoagulants sikulimbikitsidwa, popeza kuphatikiza koteroko kungakulitse kuchuluka kwa magazi. Ngakhale kugwiritsidwa ntchito kwa clopidogrel pa mlingo wa 75 mg patsiku sikusintha mbiri ya pharmacokinetic ya S-warfarin kapena kuchuluka kwazomwe zimapangidwira (INR) mwa odwala omwe amathandizidwa ndi warfarin kwa nthawi yayitali, kugwiritsa ntchito nthawi yomweyo kwa clopidogrel ndi warfarin kumawonjezera mwayi wamagazi chifukwa zodziyimira payekha pa heestasis.

Glycoprotein IIb Inhibitors, / IIIA . Clopidogrel iyenera kugwiritsidwa ntchito mosamala kwa odwala omwe ali pachiwopsezo chotaya magazi chifukwa cha kuvulala, maopaleshoni kapena zina zokhudzana ndi matenda omwe glycoprotein IIb, / IIIA inhibitors ali munthawi yomweyo.

Acetylsalicylic acid (ASA). Acetylsalicylic acid sichisintha mphamvu ya Clopidogrel ya ADP-yolowetsa kupatsidwa zinthu za m'magazi, koma Clopidogrel imawonjezera zotsatira za ASA pa collagen-invets. Komabe, kugwiritsa ntchito nthawi imodzimodziyo kwa 500 mg ya ASA 2 kawiri pa tsiku limodzi sizinachititse kuti pakhale magazi ambiri, osakhalitsa chifukwa cha clopidogrel. Popeza kuphatikiza kwa pharmacodynamic pakati pa clopidogrel ndi acetylsalicylic acid ndikotheka ndikuwonjezera magazi, munthawi yomweyo kugwiritsa ntchito mankhwalawa kumafunikira kusamala.Ngakhale izi, pali chidziwitso pakutenga clopidogrel ndi ASA pamodzi kwa chaka chimodzi.

Heparin. Zinanenedwa kuti clopidogrel sifunikira kusintha kwa heparin ndipo sikukhudza mphamvu ya heparin pakuwundana. Kugwiritsa ntchito nthawi imodzi kwa heparin sikunasinthe kufooka kwa mphamvu ya Clopidogrel pa kuphatikizidwa kwa maselo ambiri. Popeza kulumikizana kwa pharmacodynamic pakati pa clopidogrel ndi heparin ndikotheka ndikuwonjezereka kwa magazi, munthawi yomweyo kugwiritsa ntchito mankhwalawa kumafunikira kusamala.

Othandizira a thrombolytic. Chitetezo pakugwiritsa ntchito nthawi yomweyo clopidogrel, fibrin-eni kapena fibrin-enieni a thrombolytic othandizira ndi heparin amafufuzidwa mwa odwala omwe ali ndi infral myocardial infarction. Pafupipafupi magazi omwe anali ndi magazi kwambiri anali ofanana ndi omwe amapezeka munthawi yomweyo ngati mankhwala osokoneza bongo a thrombolytic ndi heparin ndi ASA.

Mankhwala osokoneza bongo a nonsteroidal anti-kutupa (NSAIDs). Kugwiritsidwa ntchito kwina kwa clopidogrel ndi naproxen akuti kukuwonjezera kuchuluka kwa magazi am'mimba omwe amatuluka. Komabe, chifukwa cha kuchepa kwa maphunziro pakukhudzana ndi mankhwalawo ndi ena a NSAID, sizikudziwikiratu, chiopsezo cha kutaya magazi m'mimba chikuwonjezeka mukamagwiritsa ntchito ndi ma NSAID onse. Chifukwa chake, kusamala ndikofunikira mukamagwiritsa ntchito NSAIDs, makamaka COX-2 inhibitors, yokhala ndi clopidogrel.

Kusankha Serotonin Reuptake Inhibitors (SSRIs). Popeza kuti ma SSRIs amakhudza kutsegula kwa magazi a m'magazi ndi kuwonjezera ngozi ya magazi, kugwiritsa ntchito nthawi yomweyo kwa SSRIs ndi clopidogrel kumafuna kusamala.

Proton Pump Inhibitors (PPIs).

The kuchuluka kwa yogwira metabolite m'magazi anachepa ndi munthawi yomweyo ntchito kapena maola 12 pakati Mlingo wa clopidogrel ndi omeprazole muyezo wa 80 mg. Kuchepetsa kumeneku kumayendetsedwa ndi kuchepa kwa kuponderezana kwa kuphatikizana kwa maplatelet. Esomeprazole akuyembekezeka kulowa mgulu lofanananso ndi clopidogrel.

Zambiri zosasangalatsa zakhala zikuwonetsa pamachitidwe a pharmacodynamic / pharmacokinetic ndi chiwopsezo cha mtima. Pankhaniyi, clopidogrel ndi omeprazole kapena esomeprazole iyenera kugwiritsidwa ntchito mosamala.

Kutsika kosatchulika mu ndende ya metabolite m'magazi kumawonedwa ndi pantoprazole kapena lansoprazole. Clopidogrel angagwiritsidwe ntchito ndi pantoprazole.

Palibe umboni kuti mankhwala ena ochepetsa asidi, monga ma proton pump blockers kapena ma antacid, amakhudza ntchito ya anti-aggregation ya clopidogrel.

Maantacid sichimakhudza kuchuluka kwa mayamwidwe a clopidogrel.

Kuphatikiza ndi mankhwala ena. Popeza clopidogrel imatembenuka kukhala yogwira metabolite pang'ono mothandizidwa ndi CYP2C19, kugwiritsa ntchito mankhwala omwe amachepetsa ntchito ya enzymeyi kungayambitse kuchepa kwa kuchuluka kwa metabolite ya clopidogrel mu plasma. Kufunika kwachipatala pakuyanjanaku sikunafotokozeredwe. Chifukwa chake, ngati njira yodzitetezera, kugwiritsa ntchito nthawi yomweyo kwa ma CYP2C19 zoletsa ayenera kupewedwa.

Kukonzekera komwe kumapangitsa kuti ntchito za CYP2C19 zikhale zamphamvu kapena zopitilira muyeso zimaphatikizapo omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, carbamazepine ndi efavirenz.

Kwambiri zamasewera mapiritsi a pharmacodynamic akamagwiritsa ntchito clopidogrel nthawi yomweyo atenolol, nifedipine kapena ndi mankhwala onse awiri sanapezeke. Kuphatikiza apo, zochita za pharmacodynamic za clopidogrel sizinasinthidwe pomwe mukugwiritsa ntchito phenobarbital ndi estrogen .

Pharmacokinetic katundu digoxin kapena theophylline sizinasinthe ndikugwiritsa ntchito nthawi imodzi ndi clopidogrel.

Carboxylic clopidogrel metabolites imatha kuletsa ntchito ya cytochrome P450 2C9.Izi zitha kuonjezera milingo ya plasma ya mankhwala ngati phenytoin ndi tolbutamide, ndi ena omwe amapukusidwa pogwiritsa ntchito cytochrome P450 2C9. Ngakhale izi, zotsatira za kafukufuku wazachipatala zimawonetsa kuti phenytoin ndi tolbutamide itha kugwiritsidwa ntchito mosavomerezeka ndi clopidogrel.

Mankhwala omwe ali gawo lapansi la cytochrome CYP2C8

Clopidogrel akuti aonjezera chiwonetsero cha repaglinide mwa odzipereka athanzi. Kugwiritsa ntchito nthawi yomweyo kwa clopidogrel ndi mankhwala omwe amapangidwa makamaka ndi CYP2C8 cytochrome (mwachitsanzo, repaglinide, paclitaxel) akuyenera kuchitika mosamala, chifukwa chowonjezera kuchuluka kwawo m'magazi a magazi.

Kupatula pachidziwitso cha kuyanjana ndi mankhwala enieni omwe tapatsidwa pamwambapa, maphunziro pazokhudzana ndi clopidogrel ndi mankhwala omwe nthawi zambiri amaperekedwa kwa odwala omwe ali ndi atherothrombosis sanachitike. Komabe, odwala omwe adatenga nawo mbali pazachipatala zama Clopidogrel adagwiritsa ntchito mankhwala ena nthawi yomweyo, kuphatikizapo okodzetsa, opanga ma beta, othandizira a ACE, othandizira calcium, mankhwala ochepetsa mafuta amkati, kuphatikiza insulin, mankhwala osokoneza bongo, mankhwala oletsa antiepileptic ndi otsutsana ndi GPIIb / IIIa, wopanda umboni wazotsatira zoyipa zovuta.