Clopidogrel teva

Sehlopha sa mahlale

Li-antithrombotic agents. Li-antiplatelet agents. Khoutu ATX B01A C04.

Thibelo ea atherothrombosis ho batho ba baholo

• ho bakuli ba nang le lefu la myocardial infarction (ho qala ha kalafo ke matsatsi a 'maloa, empa ha ho sa feta matsatsi a 35 kamora ho qala), lefu la ischemic (qalo ea kalafo ke matsatsi a 7, empa ha ho so fete likhoeli tse 6 kamora ho qala kapa ba fumanoeng ba na le lefu lena methapo ea methapo ea kutlo (Tšenyo ea methapo ea methapo ea methapo le methapo ea methapo ea likepe tse lipheletsong tse tlase),
• ho bakuli ba nang le bothata bo boholo ba 'mala o bitsoang coronary syndrome (ACS):
• le acute coronary syndrome ntle le ST karolo ea phaellano (angina e sa tsitsang kapa infroction ea myocardial ntle le leqhubu la Q), ho kenyelletsa le ho bakuli ba hlahileng nakong ea percutaneous coronary angioplasty, hammoho le acetylsalicylic acid (ASA)
• infarction ea hlobaetsang ea myocardial e nang le karolo e phahameng ea ST, hammoho le acetylsalicylic acid (ho bakuli ba fumanang meriana e tloaelehileng le ba bontšitsoeng kalafo ea thrombolytic).

Thibelo ea liketsahalo tsa atherothrombotic le thromboembolic ho atrase fibrillation:

• Clopidogrel hammoho le ASA e bontšoa ho bakuli ba baholo ba nang le fibrillation ea atrial, ba nang le bonyane kotsi e le 'ngoe ea ho hlaha ha liketsahalo tsa vascular, moo ho nang le li-contraindication tsa kalafo ka li-antagonists tsa Vitamin (AVK) le ba nang le kotsi e tlase ea ho tsoa mali, bakeng sa thibelo ea liketsahalo tsa atherothrombotic le thromboembolic ho kenyelletsa le stroke.

Tekanyetso le tsamaiso

Batho ba baholo, ho kenyeletsoa bakuli ba tsofetseng. Clopidogrel e fuoa 75 mg 1 nako e le ngoe ka letsatsi, ho sa tsotelehe lijo tse ngata.

Kalafo ea Clopidogrel ho bakuli ba nang ACS ntle le karolo ea ST e phahamisa (e sa tsitsang angina pectoris kapa infarction ea myocardial ntle le Q wave ho ECG) e qala ka lethal dose e le 'ngoe ea 300 mg, ebe u tsoela pele ka tekanyetso ea 75 mg hang ka letsatsi (le acetylsalicylic acid (ASA) ka tekanyo ea 75 325 mg / ka letsatsi. Kaha tšebeliso ea litekanyetso tse phahameng tsa ASA e eketsa menyetla ea ho tsoa mali, ho khothaletsoa hore e se ke ea feta tekanyetso ea acetylsalicylic acid ea 100 mg. Nako e nepahetseng ea kalafo ha e so theoe. Melemo ea ho sebelisa lithethefatsi ho fihlela ho likhoeli tse 12 e tlalehiloe, mme phello e phahameng e ile ea bonoa kamora likhoeli tse 3 tsa kalafo.

Ho kula ka infarction ea hlobaetsang ea myocardial e nang le sekhahla sa ST Clopidogrel e beoa 75 mg hang ka letsatsi, ho qala ka lethal dose le le leng la 300 mg hammoho le ASA, ka lithethefatsi tsa thrombolytic kapa ntle le tsona. Phekolo ea bakuli ba lilemo tse kaholimo ho 75 e qala ntle le lethal dose ea clopidogrel. Phekolo ea ho kopanya e lokela ho qaloa kapele ka mor'a ho qala ha matšoao 'me e lokela ho tsoela pele bonyane libeke tse' ne. Melemo ea ho sebelisa motsoako oa Clopidogrel le ASA bakeng sa libeke tse fetang tse 'ne ka lefu lena ha e e-so ithutoe.

Bakeng sa bakuli ba nang le fibrillation ea atrial, clopidogrel e sebelisoa ka tekanyetso e le 'ngoe ea 75 mg. Hammoho le clopidogrel, ts'ebeliso ea ASA e lokela ho qala le ho tsoela pele (ka tekanyetso ea 75-100 mg ka letsatsi).

Haeba u lahleheloa ke tekanyetso:

• Haeba nako e ka tlase ho 12:00 e fetile ho tloha nakong eo ho neng ho hlokahala hore a noe tekanyetso e latelang, mokuli o lokela ho nka lethal dose e lahlehileng hang-hang, 'me tekanyo e latelang e lokela ho nkuoa ka nako e tloaelehileng.
• Haeba ho feta 12:00 ho se ho fetile, mokuli o lokela ho nka tekanyetso e latelang ka nako e tloaelehileng empa a se ke a eketsa habeli tekanyo eo ho lefella tekanyetso e lahlehileng.

Ho hloleha hape . Phihlelo ea kalafo ea ho sebelisa lithethefatsi ho bakuli ba nang le bothata ba ho phekoloa ka methapo e lekanyelitsoe.

Ho hloleha ha sebete . Phihlelo ea kalafo ea ho sebelisa lithethefatsi ho bakuli ba nang le mafu a leka-lekaneng a sebete le monyetla oa hemorrhagic diathesis o lekanyelitsoe.

Boikutlo bo fapaneng

Ho ile ha tlalehoa hore ho tsoa mali e ne e le karabelo e tloaelehileng 'me hangata e hlaha khoeling ea pele ea kalafo.

Liphetoho tse fapaneng li ajoa har'a litho, maqhubu a ho ba teng ha tsona a hlalosoa ka tsela e latelang: khafetsa (ho tloha ³ 1/100 ho isa ho 1/10), hangata (ho tloha ho 1/1000 ho isa ≤ 1/100), ka seoelo (ho tloha ho 1/10 000 ho isa ho ≤ 1/1000), ka seoelo (litemoso Ingolise

Foromo ea litekanyetso

Matlapa a koahetsoeng ka filimi 75 mg

Letlapa le leng le na le

ntho e sebetsang: Clopidogrel hydrosulfate 97.857 mg,

e lekanang le clopidogrel 75.00 mg

li-vacipi: lactose monohydrate (200 mesh), microcrystalline cellulose (Avicel PH 101), hydroxypropyl cellulose (Klucel LF), microcrystalline cellulose (Avicel PH 112), crospovidone (Collidon CL), mofuta oa oli ea meroho ea I (Sterotex-Drite) sodium. lauryl sulfate

Sebopeho sa khetla: lactose monohydrate, hypromellose 15 cP, titanium dioxide (E171), polyethylene glycol 4000, iron oxide red (E172), iron oxide yellow (E172), indigotine (E 132, indigo carmine aluminium varnish FD&C putsoa No. 2)

Matlapa a kopantsoe le filimi ho tloha ho 'mala o mopinki ho isa ho o pinki, o bopehileng joaloka capsule, o tšoailoe "93" ka lehlakoreng le leng le "7314" ka lehlakoreng le leng.

Melemo ea pharmacological

Kamora ho tsamaisoa ka molomo, clopidogrel e kenella ka potlako ho tsoa mokokotlong oa mpa. Karolelano ea litheko tsa plasma e sa fetoheng (hoo e ka bang 2,2-2,5 ng / ml ka mor'a tekanyetso e le 'ngoe ea 75 mg) li fihlella metsotso e 45 kamora ho sebelisa moriana. Ho se be teng ka botlalo ka lebaka la ho felisoa ha masapo, 'me ho na le bonyane 50%.

Clopidogrel le metabolite ea eona ea mantlha (e sa sebetseng) e potoloha maling, li theha khokahano e khutlisetsang liprotheine tsa plasma ea motho (98% le 94%, ka ho latellana). Ho tlama ha ho na ho tlala ka mefuta e fapaneng ea likhakanyo.

Clopidogrel e fumana metabolism e matla sebeteng. Clopidogrel e tšelisoa ka litsela tse peli tsa mantlha: e 'ngoe e hokahanngoa le litheko mme e lebisa ho hydrolysis ka ho theha motsoako o sa sebetseng oa "carboxylic acid" (85% ea metabolites maling), e' ngoe e kopantsoe ke li-cytochromes tse fapaneng tsa P450. Taba ea pele, clopidogrel e tšeloa metabolite ea methapo e bohareng ea 2-oxo-clopidogrel. Ho latela metabolism ea "metabolite" e bohareng ea 2-oxo-Clopidogrel ho lebisa ho thehoeng ha metabolite e sebetsang, thiol e tsoang ho clopidogrel. Tsela ena ea metabolic e tsamaisoa ke CYP3A4, CYP2C19, CYP1A2 le CYP2B6. Metabolism e sebetsang ea thiol e tlama ka potlako le ka mokhoa o sa fetoheng liphatlalatsong tsa liplatelete, ka ho etsa joalo e thibelang ho kopana ha liplatelete.

Cmax ea metabolite e sebetsang e eketseha ka makhetlo a 2, ka bobeli ka mor'a tekanyo e le 'ngoe ea ho jarisa Clopidogrel 300 mg, mme kamora ho nka tekanyetso ea tlhokomelo ea 75 mg ka matsatsi a 4. Cmax e bonoa hoo e ka bang metsotso e 30-60 ka mor'a taolo.

Kamora ho nka koae (Clopidogrel), e ka bang 50% e ts'oeroe ka har'a moroto 'me e batla e le 46% e nang le mantle nakong ea lihora tse 120 ka mor'a taolo. Kamora tekanyetso e le 'ngoe ea molomo ea 75 mg, ho felisoa ha halofo ea bophelo ba clopidogrel hoo e ka bang lihora tse 6. Bophelo ba halofo ea metabolite ea mantlha (e sa sebetseng) e potoloha maling ke lihora tse 8 ka mor'a taolo e le 'ngoe le e pheta-phetoang.

CYP2C19 e ameha ho thehoeng ha metabolite ka bobeli le metabolite e mahareng, 2-oxo-clopidogrel. Litlamorao tsa pharmacokinetics le antiplatelet tsa metabolite e sebetsang ea Clopidogrel li fapana ho latela mofuta oa CYP2C19 genotype.

CYP2C19 * 1 allele e tsamaisana le metabolism e sebetsang ka botlalo, ha li-CYP2C19 * 2 le CYP2C19 * 3 li sa sebetse. CYP2C19 * 2 le CYP2C19 * 3 akhaonto bakeng sa boholo ba linyeoe tse nang le tšebetso e fokotsehileng ho li-metabolites tsa Europe (85%) le Asia (99%) butle. Likhakanyo tse ling tse amanang le metabolism e sieo kapa e fokotsehileng ha li sa tloaeleha ebile li kenyelletsa CYP2C19 * 4, * 5, * 6, * 7 le * 8. Ho ata ha linyeoe tsa CYP2C19, ho hlahisang metabolism e leka-lekaneng le e liehang ea CYP2C19, ho ne ho fapana ho latela morabe / morabe. Lintlha tse lekanyelitsoeng tsa lingoliloeng li fumaneha bakeng sa baahi ba Asia, tse sa re lumelle ho lekola phello ea CYP2C19 genotyping mabapi le sephetho sa tleleniki ea liketsahalo.

Mokuli ea nang le boemo ba metabolizer e liehang o tla ba le mahlakore a mabeli a nang le ts'ebetso e lahlehileng, joalo ka ha ho hlalositsoe kaholimo. Khafetsa ea genotype ea metabolism e liehang ea CYP2C19 e batla e le 2% bakeng sa batho ba Europe, 4% ea morabe oa Afrika le 14% ea matsoalloa a China. Ho na le liteko tsa ho tseba mofuta oa mokuli oa CYP2C19.

Ho ne ho se na phapang e kholo ea ho pepesetsoa metabolite e sebetsang le ka har'a khatello e tloaelehileng ea platelet aggregation (PAT) lipakeng tsa metabolraf e potlakileng le e mahareng. Ka li-metabolites tse liehang, ho pepesetsoa ha metabolite e sebetsang ho fokotsehile ka 63-71% ha ho bapisoa le metabolites e potlakileng. Kamora ho sebelisa regimen ea 300 mg / 75 mg, ho fokotseha ha karabelo ea antiplatelet ho metabolite e liehang ho bonoa, ha PAT (5 μM ADP) e le 24% (lihora tse 24) le 37% (letsatsi la 5) ha e bapisoa le 39% PAT (lihora tse 24) ) le 58% (letsatsi la 5) ea metabolites e potlakileng le 37% (lihora tse 24) le 60% (letsatsi la 5) ea li-metabolites tse mahareng. Ha li-metabolites tse liehang ho feta li-regimen tsa 600 mg / 150 mg, ho pepesetsoa metabolite e sebetsang ho kholo ho feta ho regimen ea 300 mg / 75 mg. Ntle le moo, PAT ke 32% (lihora tse 24) le 61% (letsatsi la 5), ​​e fetang eo ea li-metabolites tse liehang ho li-regimen tsa 300 mg / 75 mg, empa tse ts'oanang le lihlopha tse ling tsa li-metabolic tsa CYP2C19 tse ho 300 mg / 75 regimen mg Mokhoa o nepahetseng oa litekanyetso tsa batho bana ba nang le mamello ha o e-so thehoe.

Ho pepesetsoa metabolite e sebetsang ho fokotsoe ke 28% ho li-metabolites tse mahareng le ka 72% ho li-metabolic tse liehang, ha khatello ea li-platelet aggregation (5 μM ADP) e fokotseha ka phapang ho PAT ea 5.9% le 21.4%, ka ho latellana, ha e bapisoa le ka potlako. metabolism.

Li-pharmacokinetics tsa metabolite e sebetsang ea Clopidogrel ho tsena (tse nang le ts'ebetso ea sebete le ts'ebetso ea meno) bongata bo ikhethang ha bo tsejoe.

Ts'ebetso ea mokokotlo e sa sebetseng

Kamora litekanyetso tsa khafetsa tsa Clopidogrel ho 75 mg ka letsatsi ho bakuli ba nang le lefu le matla la liphio (clearinine clearance ho tloha ho 5 ho isa ho 15 ml / min), khatello ea methapo ea methapo e bakoang ke ADP (adenosine diphosphate) e fokola (25%) ho feta lithutong tse phetseng hantle. ho tsoa mali ho tšoana le nako ea ho tsoa mali lithutong tse phetseng hantle tse amohetseng 75 mg ea clopidogrel ka letsatsi. Ntle le moo, ho na le mamello e ntle ea kliniki ho bakuli bohle.

Ts'ebetso ea sebete e sa sebetseng

Kamora litekanyetso tsa khafetsa tsa Clopidogrel ho 75 mg ka letsatsi bakeng sa matsatsi a 10 ho bakuli ba nang le ts'ebetso ea sebete e matla, thibelo ea bongata ba liplatelese tse bakoang ke ADP e ts'oana le litaba tse phetseng hantle. Nako e telele ea nako ea ho tsoa mali lihlopheng tsena ka bobeli le eona ha e fetohe.

Clopidogrel ke selelekela sa ntho e sebetsang, e 'ngoe ea li-metabolites tseo e leng thibelo ea lintho tse ngata tse entsoeng ka masapo.Clopidogrel e tšelisoa ke li-enzyme tsa CYP2C19, e leng se hlahisang sebopeho sa metabolite e sebetsang e thibelang bongata ba liplatelete. Clopidogrel metabolite e sebetsang e thibela ho kopanya ha adenosine diphosphate (ADP) ho pokello ea mokokotlo oa mokokotlo oa P2Y12 le ts'ebetso e latelang ea GPIIb / IIIa glycoprotein tata ka lebaka la ADP, ka ho etsa joalo e thibela liplatelese tsa bongata. Ka lebaka la ho se khone ho hlophisoa, liplatelese tse amehang li senyeha bophelo bohle ba tsona (matsatsi a ka bang 7-10), mme ts'ebetso e tloaelehileng ea liplatelete e khutlisoa ka sekhahla se lumellanang le potoloho ea liplatelete. Phatlalatso ea liplatelete e bakoang ke li-agonists ntle le ADP e boetse e hatelloa ka ho thibela ho eketsoa ha ts'ebetso ea liplatelete ka ho pepesetsoa ADP e lokollotsoeng.

Kaha metabolite e sebetsang e thehiloe ho sebelisoa li-enzyme tsa CYP450, tseo tse ling tsa tsona e leng li-polymorphic kapa tse hatisitsoeng ke metsoako e meng ea meriana, ha se bakuli bohle ba nang le degree ea khatello ea methapo e lekaneng.

Litekanyetso tse pheta-phetoang tsa 75 mg ka letsatsi ho tloha ka letsatsi la pele li lebisa ho thibelo e kholo ea pokello ea liplatelete e bakoang ke ADP. Phello ea inhibitory e eketseha butle-butle mme e fihla boemong ba tekano ka matsatsi a 3-7. Boemong ba tekano, tekanyetso ea thibelo e bonoa ka tekanyetso ea 75 mg ka letsatsi mme e tloha ho 40% ho isa ho 60%. Phatlalatso ea polasetiki le nako ea ho tsoa mali butle-butle e khutlela boemong ba eona ba pele, hangata matsatsi a 5 kamora hore kalafo e hlakoloe.

Thibelo ea liketsahalo tsa atherothrombotic:

- ho bakuli ba nang le myocardial infarction (ho tloha matsatsing a 'maloa ho fihlela

Tekanyetso le tsamaiso

Clopidogrel-Teva e laetsoe ka molomo ho sa tsotelehe menyetla ea lijo.

Bakeng sa bakuli le bakuli ba tsofetseng, Clopidogrel-Teva e laetsoe ka tekanyetso e le 'ngoe ea 75 mg.

Ho hlobaetsang le coronary syndrome ntle le ho phahamisa karolo ea ST (e sa tsitsang angina kapa myocardial infarction ntle le maqhubu a Q), moriana o fanoa ka lethal dose le le leng la 300 mg. Motsoako oa ho lokisa ke 75 mg ka letsatsi (hammoho le asiti ea acetylsalicylic ho 75th25 mg / ka letsatsi) bakeng sa likhoeli tse 12. Phello e phahameng ea kalafo e bonoa kamora likhoeli tse 3. Ha ho kgothaletswe ho feta tekanyetso ea acetylsalicylic acid ho feta 100 mg, ka lebaka la kotsi e eketsehileng ea ho tsoa mali.

Ho infarction e mpe ea myocardial le keketseho ea karolo ea ST, moriana o laetsoe ka tekanyetso ea 75 mg ka letsatsi (hammoho le acetylsalicylic acid) ho qala ka lethal dose le le leng la 300 mg, ka lithethefatsi kapa ntle le thrombolytic. Ho bakuli ba kaholimo ho lilemo tse 75, kalafo ea Clopidogrel-Teva e etsoa ntle le tšebeliso ea tekanyetso e le 'ngoe ea ho jarisa. Phekolo ea ho kopanya e lokela ho qaloa kapele ka mor'a ho qala ha matšoao mme e tsoele pele bonyane libeke tse 4.

Ka fibrillation ea atrial, moriana o beoa e le lethal dose le le leng la 75 mg, hammoho le acetylsalicylic acid 75-100 mg ka letsatsi.

Haeba u tlola ho sebelisa lithethefatsi tse ka tlase ho lihora tse 12 ho tloha kemisong e tloaelehileng, mokuli o lokela ho nka tekanyetso hanghang, 'me ka mor'a moo a noe tekanyetso e latelang ka nako e tloaelehileng. Haeba ho se ho fetile lihora tse 12, mokuli o lokela ho nka tekanyetso ea moriana ka nako e tloaelehileng, ha a lokela ho nka tekanyetso e habeli.

Ts'ebetso ea mokokotlo e sa sebetseng

Phihlelo ea kalafo ea Clopidogrel ho bakuli ba nang le ts'ebetso ea renal e haelloang. Ka hona, maemong a bakuli ba joalo, moriana o lokela ho sebelisoa ka hloko.

Ts'ebetso ea sebete e sa sebetseng

Phihlelo ea ts'ebeliso ea lithethefatsi ho bakuli ba nang le bothata ba sebete bo sa sebetseng hantle, bo tloaeloang ho hemorrhagic diathesis, ha e na meeli. Mabapi le sena, ho bongata bona, moriana o lokela ho sebelisoa ka hloko.

Litlamorao

Ho tšolla mali ke mokhoa o atileng haholo o tlalehiloeng litekong tsa tleliniki le ka mora nako ea ho bapatsa, moo ho neng ho tlalehiloe haholo khoeling ea pele ea kalafo.

Liphetoho tse mpe tse hlokometsoeng litekong tsa bongaka kapa tse tlalehiloeng litlalehong tsa boithati li thathamisitsoe ka tlase.

Contraindication

- Hypersensitivity ho ntho e sebetsang kapa ho dikarolo tsa moriana

- ho hloka matla ha sebete

- Ho tsoa mali ka mpeng (leqeba la ka mpeng, ho ruruha ha methapo ea letsoho)

- ho se mamellane ha galactose, khaello ea Lappase ea lactase kapa malabsorption ea glucose-galactose

- boimana le ho nyeka

- bana ba ka tlase ho lilemo tse 18

Ho sebelisana le lithethefatsi

Li-anticoagulants tsa molomo: tšebeliso ea nako e tšoanang ea clopidogrel ka li-anticoagulants tsa molomo ha e khothalletsoe, kaha motsoako ona o ka eketsa mali. Leha taba ea hore ho nka 75 mg ea clopidogrel ka letsatsi ha e fetole pharmacokinetics ea S-warfarin kapa karolelano e tloaelehileng ea machabeng (INR) ho bakuli ba nkang warfarin nako e telele, ts'ebeliso e le 'ngoe ea clopidogrel le warfarin e eketsa kotsi ea ho tsoa mali ka lebaka la litlamorao tsa bobeli ho hemostasis sethethefatsi.

Glycoprotein IIb / IIIa inhibitors: clopidogrel e lokela ho sebelisoa ka hloko ho bakuli ba fumanang li-inhibitors tsa IIb / IIIa glycoprotein ka nako e tšoanang.

Acetylsalicylic acid (ASA): ASA ha e fetole thibelo ea bohloka ba plopidogrel e hlahisitsoeng ke ADP, empa Clopidogrel e ntlafatsa phello ea ASA ho mokelikeli oa liplatelete tse hlahisitsoeng ke collagen. Leha ho le joalo, tsamaiso e le 'ngoe ea ASA ho 500 mg habeli ka letsatsi ho pholletsa le letsatsi ha e bake keketseho e kholo ea nako ea ho tsoa mali ka lebaka la clopidogrel. Pakeng tsa clopidogrel le acetylsalicylic acid, ts'ebelisano ea pharmacodynamic e ka etsahala, e lebisang kotsing e kholo ea ho tsoa mali. Ka hona, ts'ebeliso e tšoanang ea meriana ena e lokela ho etsoa ka hloko. Le ha ho le joalo, Clopidogrel le ASA li ngolisitsoe hammoho nako e ka etsang selemo.

Heparin: clopidogrel ha e hloke phetoho ea tekanyetso ea heparin kapa ha e ame phello ea heparin ho kopaneng ea mali. Ho sebelisoa ha heparin ka nako e le 'ngoe ha ho ame ho sitisoa ha ho kopana ha liplatelete ho bakoang ke clopidogrel. Pakeng tsa clopidogrel le heparin, ts'ebelisano ea pharmacodynamic e ka etsahala, e lebisang kotsing e kholo ea ho tsoa mali. Ka hona, ts'ebeliso e tšoanang ea meriana ena e lokela ho etsoa ka hloko.

Basebeletsi ba Thrombolytic: polokeho ea tšebelisano ea li-clopidogrel tse nang le li-protrin tse itseng tse khethehileng le tse sa tobang tsa fibrinolytic le heparins li ithutile ho bakuli ba nang le infarction e mpe ea myocardial. Khafetsa khafetsa ho tsoa mali ka kliniki e lula e ts'oana le e bonoang ka tšebeliso ea li-arhente tsa thrombolytic le heparin hammoho le ASA.

Lithethefatsi tse seng khahlanong le ho ruruha (NSAIDs): ts'ebeliso e kopaneng ea clopidogrel le naproxen li eketsa tahlehelo ea mali e tsoang methapong ea mpa. Leha ho le joalo, ka lebaka la khaello ea lithuto tse lekaneng tsa kliniki mabapi le ho sebelisana le li-NSAID tse ling, hajoale ha ho hlake hore na menyetla e eketsehileng ea ho tsoa mali ka mpeng ke tšobotsi ea liNSAID tsohle. Ka hona, ts'ebeliso e tšoanang ea NSAIDs (ho kenyelletsa COX-2 inhibitors) le clopidogrel e hloka tlhokomeliso.

Pheko e 'ngoe e tšoanang: kaha clopidogrel e tšelisoa metabolite ea eona e sebetsang e sebelisa CYP2C19, ho lebelletsoe hore tšebeliso ea lithethefatsi tse hatellang ts'ebetso ea enzyme ena e tla lebisa ho fokotseha ha maikutlo a lithethefatsi tsa metabolite e sebetsang ea clopidogrel. Bohlokoa ba bongaka ba tšebelisano ena ha bo hlake.Joaloka tšireletso, tšebeliso e tšoanang ea lithethefatsi tse hatellang CYP2C19 e lokela ho lahloa.

Mithethefatsi e hatellang CYP2C19 e kenyeletsa omeprazole le esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine le chloramphenicol.

Proton Pump Inhibitors (PPIs):

Omeprazole ka tekanyo ea 80 mg hang ka letsatsi, e nooa ka nako e le ngoe le clopidogrel, kapa nako ea lihora tse 12 pakeng tsa litekanyetso tsa lithethefatsi tse peli, e fokotsa tlhahiso ea metabolite e sebetsang ka 45% (lethal dose) le 40% (lethal dose). Ho fokotseha ho tsoa ho 39% (lethal dose ea ho laolla) le 21% (tekanyetso ea tlhokomelo) ho tsamaisana le ho fokotseha ha khatello ea khatello ea mali. Esomeprazole, e nkuoe ka nako e le 'ngoe le clopidogrel, e boetse e lebelletsoe ho fokotsa ho pepeseha ha metabolite e sebetsang. Joaloka ts'ireletso, omeprazole kapa esomeprazole ha ea lokela ho sebelisoa ka nako e le ngoe le clopidogrel.

Phokotso e tlase e boletsoeng ea ho pepeseha ha metabolite e bonoa maemong a pantoprazole le lansoprazole.

Metsoako ea plasma ea metabolite e sebetsang e fokotsoa ke 20% (lethal dose) le 14% (tekanyetso ea tlhokomelo) nakong ea kalafo le pantoprazole ka tekanyo ea 80 mg hang ka letsatsi. Sena se tsamaisana le ho fokotseha ha thibelo ea bongata ba liplatelete ka 15% le 11%, ka ho latellana. Sena se bolela hore clopidogrel e ka sebelisoa le pantoprazole.

Ha ho na bopaki ba hore lithethefatsi tse ling tse fokotsang acid ea tumbo tse kang H2 receptor blockers (ntle le cimetidine, e leng CYP2C19 inhibitor) kapa li-antacid, li kena-kenana le ts'ebetso ea antiplatelet ea clopidogrel.

Meriana e meng:

Ha ho na litšebelisano tsa bohlokoahali tsa pharmacodynamic ha o nka clopidogrel ka atenolol kapa nifedipine kapa ka lintho tsena ka bobeli. Ts'ebeliso e ts'oanang ea phenobarbital kapa estrogen le eona ha e ame mosebetsi oa Clopidogrel oa pharmacodynamic haholo.

Li-pharmacokinetics tsa digoxin le theophylline ha li fetohe ka tšebeliso e le 'ngoe ka clopidogrel.

Li-antacid ha li fetole boemo ba ho monngoa ha Clopidogrel.

Phenytoin le tolbutamide, e entsoeng ka CYP2C9, e ka sebelisoa ka polokeho ka clopidogrel.

Lithuto tsa tšebelisano ea "clopidogrel" le lithethefatsi tse ling, tseo hangata li laeloang bakuli ba nang le atherothrombosis (ntle le lithethefatsi tse boletsoeng ka holimo), ha li e-so tšoaroe. Leha ho le joalo, ho bakuli ba nkang liteko tsa tleliniki ea Clopidogrel ea neng a e-na le lithethefatsi tse fapaneng, ho ne ho se na litšebelisano tsa bohlokoa ka tliliniki. Lithethefatsi tsena li kenyelletsa diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), antagonists ea calcium, lithethefatsi tse fokotsang k'holeseterole, li-vasodilators tsa coronary, lithethefatsi tsa antidiabetic (ho kenyeletsa insulin), lithethefatsi tsa antiepileptic, hammoho le li-blockers tsa GPII Li-receptors tsa IIIa.

Litaelo tse khethehileng

Ho tsoa mali le mathata a hematological

Ka lebaka la kotsi ea ho tsoa mali le karabelo e mpe ea hematological nakong ea kalafo, haeba matšoao a kliniki a fana ka maikutlo a ho tsoa mali, tlhahlobo e akaretsang ea mali le / kapa liteko tse ling tse nepahetseng li lokela ho etsoa hang-hang. Joalo ka li-antiplatelet agents tse ling, clopidogrel e lokela ho sebelisoa ka hloko ha bakuli ba ka ba kotsing ea ho tsoa mali ho amanang le ho sithabela maikutlo, ho buuoa kapa maemo a mang a methapo, hammoho le ho bakuli ba tšoaroang ke ASA, heparin, IIb glycoprotein inhibitors / III kapa lithethefatsi tse seng khahlanong le ts'oaetso tsa antiidal (NSAIDs), ho kenyelletsa le li-inhibitors tsa COX-2. Bakuli ba lokela ho hlahlojoa ka hloko bakeng sa matšoao afe kapa afe a ho tsoa mali, ho kenyelletsa le ho tsoa mali ka matla a phahametseng tlhaho, haholo-holo libekeng tsa pele tsa kalafo le / kapa ka mor'a lits'ebetso tsa pelo tse hlaselang kapa ho buuoa.Tšebeliso e tšoanang ea clopidogrel e nang le li-anticoagulants tsa molomo ha e khothalletsoe, kaha sena se ka eketsa mali.

Haeba mokuli a tlameha ho kenella ts'ebetsong ea bongaka e khethiloeng, mme phello ea antiplatelet ha e lakatsehe ka nakoana, clopidogrel e lokela ho khaoloa matsatsi a 7 pele ho buuoa. Pele ho buuoa leha e le hofe ho reriloeng le ho sebelisa sethethefatsi leha e le sefe se secha, bakuli ba lokela ho lemosa lingaka tsa bongaka hore li ntse li nka Clopidogrel.

Clopidogrel e lelefatsa nako ea ho tsoa mali mme e lokela ho sebelisoa ka hloko ho bakuli ba nang le liphetoho tsa methapo ea methapo ea methapo ea mali ho tsoa maling (haholo-holo gastrointestinal le intraocular).

Bakuli ba lokela ho tsebisoa hore ha ba nka Clopidogrel-Teva (a le mong kapa a kopane le ASA), ho ka nka nako e telele ho emisa ho tsoa mali, le hore ba lokela ho tsebisa ngaka ea bona haeba ba e-ba le ho tsoa mali ho sa lebelloang (ka sebaka kapa nako) .

Thrombotic Thrombocytopenic Purpura (TTP)

Ka seoelo, linyeoe tsa thrombotic thrombocytopenic purpura (TTP) li tlalehiloe kamora ts'ebeliso ea lithethefatsi Clopidogrel-Teva, 'me ka linako tse ling ka mor'a ho pepesetsoa hanyane. E tšoauoa ka thrombocytopenia le phallo ea methapo ea methapo ea methapo, e tsamaeang le liphetoho tsa methapo, ho hlohlona ha lesapo la mokokotlo, kapa feberu. TTP ke boemo bo behang bophelo kotsing bo hlokang kalafo e potlakileng, ho kenyelletsa plasmapheresis.

Ho tlalehiloe hore ho nka Clopidogrel ho lebisa ho holiseng hemophilia e fumanoeng. Monyetla oa ho ba le hemophilia e fumanoeng o lokela ho nahanoa ka keketseho e ikhethileng ea nako e sa sebetseng ea mofuta oa thromboplastin (APTT), kapa o sena madi. Phekolo ea bakuli ba nang le ts'oaetso e netefalitsoeng ea hemophilia e fumanoeng le ho lekola maemo a bona e lokela ho etsoa ke litsebi, mme clopidogrel e lokela ho khaotsa.

Haufinyane tjena ischemic stroke

Ka lebaka la khaello ea tlhaiso-leseling, lithethefatsi li ke ke tsa khothaletsoa matsatsing a 7 a pele ka mor'a ho otloa ke lefu la sethoathoa haholo.

Cytochrome P450 2C19 (CYP2C19)

Pharmacogenetics: Ho bakuli ba fokotsang CYP2C19 metabolites, clopidogrel e hlahisa metabolites e sa sebetseng ho litekanyetso tse khothalelitsoeng, mme e na le phello e nyane ts'ebetsong ea platelet. Ho na le liteko tse lokelang ho fumanoa ho bakuli ba nang le mofuta oa CYP2C19 genotype.

Ho tloha ha ho thehoa li-metabolite tsa "clopidogrel" tse sebetsang, ka karolo e 'ngoe, le ho nka karolo ha CYP2C19, ho lebelletsoe hore tšebeliso ea meriana e thibelang ketso ea enzyme ena e tla lebisa ho fokotseha hoa khatello ea metabolites e joalo. Bohlokoa ba ts'ebelisano ena ha bo e-so tsejoe. Joaloka tšireletso, ts'ebeliso ea li-inhibitors tse matla kapa tse mahareng tsa CYP2C19 ha e khothalletsoe ka nako e ts'oanang le ena lithethefatsi.

Allergic Cross Reactivity

Kaha tšebeliso ea sefapano e lebisang ho karabelo ea mafua ho tlalehiloe thienopyridine, ho lokela ho hlahlojoa hore na mokuli o na le nalane ea hypersensitivity ho li-thienopyridine tse ling, tse kang ticlopidine le prasugrel. Ho bakuli ba nang le nalane ea hypersensitivity ho li-thienopyridine tse ling, tlhokomelo e lokela ho beoa leihlo ka hloko nakong ea kalafo bakeng sa matšoao a hypersensitivity ho clopidogrel.

Ts'ebetso ea mokokotlo e sa sebetseng

Phihlelo ea kalafo ea Clopidogrel ho bakuli ba nang le ts'ebetso ea renal e haelloang. Ka hona, maemong a bakuli ba joalo, moriana o lokela ho sebelisoa ka hloko.

Ts'ebetso ea sebete e sa sebetseng

Phihlelo ea ts'ebeliso ea lithethefatsi ho bakuli ba nang le bothata ba sebete bo sa sebetseng hantle, bo tloaeloang ho hemorrhagic diathesis, ha e na meeli. Mabapi le sena, ho bongata bona, moriana o lokela ho sebelisoa ka hloko.

Bokhachane le pelehi

Ka lebaka la khaello ea tlhaiso-leseling ka litlamorao tsa Clopidogrel nakong ea kemolo, ho bohlokoa hore u se ke ua sebelisa clopidogrel nakong ea kemolo e le mokhoa oa ho ba hlokolosi.

Boithuto ba pelehi ha bo a hlahisa litla-morao life tse sa tobang kapa tse sa tobang tsa lithethefatsi ho ima, nts'etsopele ea "embryonic / fetus"

Ha ho tsejoe hore na Clopidogrel e fetela lebeseng la motho. Boithuto ba preclinical bo bontšitse hore Clopidogrel e fetela lebese la matsoele. E le mokhoa oa ho qoba, ho anyesa ha hoa lokela ho tsoelapele nakong ea kalafo ka clopidogrel-Teva.

Boithuto ba preclinical ha bo bontše hore Clopidogrel e ama tsoalo.

Lintlha tsa phello ea lithethefatsi ho bokhoni ba ho khanna koloi kapa mekhoa e ka bang kotsi

Ka lebaka la tšubuhlellano ea ho ba le tšubuhlellano kapa litlamorao tse sa tloaelehang haholo, lithethefatsi li lokela ho sebelisoa ka hloko ha o khanna le mochini o sebetsang.

TLHALOSO MABAKA

BarekingSar. Clopidogrel ka boomo e thibela ho tlama ha ADP ho li-receptor tsa liplatelete le ho kengoa tšebetsong ha glycoprotein (GP) IIb / IIIa tataiso 'me ka hona e sitisa pokello ea liplatelete. Clopidogrel e boetse e thibela ho kopana ha liplatelete ho bakoang ke lintho tse ling. Lithethefatsi ha li ame tšebetso ea PDE.

Clopidogrel ha e fetohe ka mokhoa o feto-fetohang oa liplatelete tsa ADP, mabapi le hore liplatelete li lula li sa sebetse bophelo bohle, mme ho tsosolosoa ha ts'ebetso e tloaelehileng ho etsahala kamora ho nchafatsoa hoa liplatelete (hoo e ka bang matsatsi a 7). Boemo bo bohlokoa ba ho thibela liplatelete ka lipalo le ka mokhoa o hlakileng oa liplatelete bo lemohile lihora tse 2 kamora ho tsamaisoa ha molomo ka tekanyetso e le 'ngoe ea clopidogrel. Tsamaiso e pheta-phetoang ea lethal dose ea 75 mg e lebisa ho thibelo e kholo ea ho kopana ha liplatelete. Tšusumetso e mpefala butle-butle, 'me boemo bo tsitsitseng bo fihlelleha kamora matsatsi a 3-7. Ho feta moo, sekhahla sa thibelo ea ho kopanya tlasa ts'usumetso ea lethal dose ea 75 mg ke 40-60%. Ho kopana ha liplatelete le nako ea ho tsoa mali ho khutlela metheong ka kakaretso matsatsi a 7 kamora ho emisa Clopidogrel.

Mofumahali Kamora ho nka tekanyetso ea 75 mg, clopidogrel e kenella ka potlako mokokotlong oa lijo. Leha ho le joalo, khatello ea eona ho plasma ea mali ha e na taba ebile kamora lihora tse peli kamora ts'ebetso ha e fihle moeli oa tekanyo (0.025 μg / l).

Clopidogrel e kenngoa ka potlako maling. Metabolite ea eona e kholo e tsoa ho carboxylic acid mme e etsa karolo ea 85% ea motsoako o potileng ka plasma ea mali. C_max ea metabolite ena ka plasma ea mali ka mor'a tekanyetso e khutsitseng ea Clopidogrel ka tekanyo ea 75 mg e ka bang 3 mg / l mme e fihlella hora e le 'ngoe ka mor'a ts'ebetso.

Pharmacokinetics ea metabolite ea mantlha e bonts'itse kamano ea moeli kahare ho lethathamo la litekanyetso tsa clopidogrel 50-150 mg. Clopidogrel le metabolite ea eona e ka sehloohong li ikamahanya le liprotheine tsa plasma ka vitro (98 le 94%, ka ho latellana). Tlamo ena e lula e sa kopantsoe le vitro ka holim'a mefuta e mengata.

Kamora ho nka, 50% ea lethal dose e nkuoeng e hloelisoa ka har'a moroto le 46% e nang le mantle nakong ea lihora tse 120 ka mor'a taolo. T_½ metabolite e ka sehloohong ke lihora tse 8

Khatello ea metabolite e ka sehloohong plasma ea mali e phahame haholo ho bakuli ba tsofetseng (ba fetang lilemo tse 75) ha ba bapisoa le baithaopi ba bacha ba phetseng hantle. Leha ho le joalo, ho tsepamisa mohopolo oa plasma e phahameng ho ne ho sa tsamaisane le liphetoho mokhoeng oa ho kopanya liplakate le nako ea ho tsoa mali. Khokahano ea metabolite ea mantlha ho plasma ea mali ha e nkuoa 75 mg / ka letsatsi e theohile haholo ho bakuli ba nang le lefu le matla la liphio (creatinine clearance (CC) 5-15 ml / min) ha ba bapisoa le bakuli ba nang le lefu la methapo e leka-lekaneng (CC 30-60 ml / min) ) le baithaopi ba phetseng hantle.Le ha phello ea inhibitory ho motsoako oa methapo ea methapo ea ADP e fokotsoe (25%) ha e bapisoa le baithaopi ba phetseng hantle, nako ea ho tsoa mali e ne e le telele ho lekana le baithaopi ba phetseng hantle ba amohetseng Clopidogrel ka tekanyo ea 75 mg / ka letsatsi.

thibelo ea lipontšo tsa atherothrombosis ho batho ba baholo:

• ho bakuli kamora lefu la myocardial (tšimoloho ea kalafo - matsatsi a 'maloa hamorao, empa ha ho sa feta matsatsi a 35 kamora ho qala), lefu la ischemic (tšimoloho ea kalafo - matsatsi a 7, empa kamora likhoeli tse 6 kamora ho qala) kapa ka lefu le fumanoeng le le tšoaetsanoang. methapo ea pelo (Tšenyo ea methapo ea methapo le methapo ea methapo ea lijana tse lipheletsong tse tlase),
• ho bakuli ba nang le bothata bo boholo ba 'mala o bitsoang coronary syndrome (ACS):
• le ACS ntle le ho phahamisa karolo ea S - T (e sa tsitsang ea angina pectoris kapa myocardial infarction ntle le leqhubu la Q), ho kenyelletsa le ho bakuli ba ileng ba ts'oaroa nakong ea percutaneous coronary angioplasty, hammoho le acetylsalicylic acid,
• ka infarate ea myocardial e hlobaetsang le ho phahama ha sekhahla sa S - T, hammoho le acetylsalicylic acid (ho bakuli ba fumanang meriana e tloaelehileng le ba bontsitsoeng kalafo ea thrombolytic).

Thibelo ea liketsahalo tsa atherothrombotic le thromboembolic tse nang le fibrillation ea atomy: clopidogrel hammoho le acetylsalicylic acid e bontšoa ho bakuli ba baholo ba nang le fibrillation ea atical, ba nang le bonyane kotsi e le 'ngoe ea ho hlaha ha liketsahalo tsa vascular, contraindication ho kalafo le bahanyetsi ba mali ba K, le kotsi e tlase ea prophylaxis e nang le methapo ea mali le ts'oaetso ea mali. le liketsahalo tsa thromboembolic, ho kenyelletsa le stroke.

TPLELISO

batho ba baholo, ho kenyeletsa bakuli ba tsofetseng. Clopidogrel e fuoa 75 mg 1 nako e le ngoe ka letsatsi, ho sa tsotelehe lijo tse ngata.

Phekolo ea Clopidogrel ea bakuli ba nang le ACS ntle le ho phahamisa karolo ea S - T (e sa tsitsang ea angina pectoris kapa myocardial infarction ntle le Q wave ho ECG) e qala ka lethal dose le le leng la 300 mg, ebe o tsoela pele ka tekanyo ea 75 mg hang ka letsatsi (acid e acetylsalicylic ka tekanyo ea 75- 325 mg / letsatsi). Kaha tšebeliso ea litekanyetso tse phahameng tsa asiti e nang le acetylsalicylic acid e eketsa menyetla ea ho tsoa mali, ho khothaletsoa hore e se ke ea feta tekanyo ea 100 mg. Nako e nepahetseng ea kalafo ha e so theoe. Melemo ea ho sebelisa lithethefatsi ho fihlela ho likhoeli tse 12 e tlalehiloe, mme phello e phahameng e fumanoe kamora likhoeli tse 3 tsa kalafo.

Bakeng sa bakuli ba nang le infarate ea myocardial e hlobaetsang le ho phahamisoa ha sekhahla sa S - T, Clopidogrel e fuoa 75 mg hang ka letsatsi, ho qala ka lethal dose le le leng la 300 mg ho kopantsoe le acetylsalicylic acid, ka lithethefatsi kapa ntle le thrombolytic. Phekolo ea bakuli ba kaholimo ho lilemo tse 75 e qala ntle le lethal dose ea clopidogrel. Phekolo ea ho kopanya e lokela ho qaloa kapele ka mor'a ho qala ha matšoao mme e tsoele pele bonyane libeke tse 4. Melemo ea ho sebelisa motsoako oa Clopidogrel le asiti ea acetylsalicylic bakeng sa libeke tse fetang tse 4 ha e so ithutoe ka lefu lena.

Bakeng sa bakuli ba nang le fibrillation ea atrial, clopidogrel e sebelisoa ka tekanyetso e le 'ngoe ea 75 mg. Hammoho le clopidogrel, ts'ebeliso ea acetylsalicylic acid e lokela ho qala le ho tsoela pele (ka tekanyo ea 75-100 mg / ka letsatsi).

Haeba u lahleheloa ke tekanyetso:

• Haeba ho se ho fetile lihora tse 12 ho tloha nakong eo ho hlokahalang hore u nke moriana o latelang, mokuli o lokela ho nka lethal dose hang-hang ka nako e tloaelehileng.
• haeba ho se ho fetile lihora tse 12, mokuli o lokela ho nka tekanyetso e latelang ka nako e tloaelehileng, empa a se ke a pheta tekanyetso habeli ho fumana tefo ea moriana o lahlehileng.

Ho hloleha hape Phihlelo ea kalafo ea ho sebelisa lithethefatsi ho bakuli ba nang le bothata ba ho phekoloa ka methapo e lekanyelitsoe.

Ho hloleha ha sebete. Phihlelo ea kalafo ea ho sebelisa lithethefatsi ho bakuli ba nang le mafu a lekaneng a sebete le kotsi ea hemorrhagic diathesis e lekanyelitsoe.

LITLHAKUOE

ho tsoa mali ho tlalehiloe e le mokhoa o tloaelehileng o fapaneng oa ho arabela mme hangata o hlahile ka khoeli ea pele ea kalafo.

Liphetoho tse fapaneng li ajoa har'a litho, maqhubu a ho ba teng ha tsona a hlalosoa ka tsela e latelang: khafetsa (ho tloha ≥1 / 100 ho isa ≤1 / 10), hangata (ho tloha ≥1 / 1000 ho ≤1 / 100), ka seoelo (ho tloha ≥1 / 10,000 ho isa ho ≤ 1/1000), ka seoelo (ho tsoa lits'ebetsong tsa ho potoloha le ho ruruha hoa mmele: ka seoelo - thrombocytopenia, leukopenia, eosinophilia, neutropenia, ho kenyelletsa le neutropenia e matla, ka seoelo haholo - thrombotic thrombocytopenic purpura, anemia ea aplasiki, pancytopenia, agranulocytosis, .

Karolong ea sesole sa 'mele: ke ka seoelo - bokuli ba serum, maikutlo a anaphylactoid, a sa tsejoeng - sefapano-hypersensitivity lipakeng tsa thienopyridine (joalo ka ticlopidine, prasugrel) (bona LITLHAKISO TSA BOTSOANG).

Ho tsoa ho psyche: ka seoelo - hallucinations, pherekano.

Ho tsoa ts'ebetsong ea methapo: ka seoelo - ho tsoa mali ho intracranial (maemong a mang, ho bolaea), hlooho ea hlooho, paresthesia, kizungu, haholo ka seoelo - phetoho ea tatso.

Ho tloha lehlakoreng la setho sa pono: khafetsa - ho tsoa mali sebakeng sa leihlo (conjunctival, ocular, retinal).

Ka lehlakoreng la setho se utloang: ka seoelo - kizunguzungu.

Ho tsoa likepeng: khafetsa - hematoma, ka seoelo - bohlokoa ba hemorrhage, ho tsoa mali ho tsoa leqebeng le ts'ebetsong, vasculitis, arterial hypotension

Ho tloha ts'ebetsong ea ho phefumoloha: khafetsa - nosebleeds, ka seoelo - ho tsoa mali ka har'a pampiri ea ho phefumoloha (hemoptysis, pulmonary hemorrhage), bronchospasm, pneumonitis e ka hare ho nako, pneumonia.

Ho tsoa ho tsamaiso ea tšilo ea lijo: hangata - ho tsoa mali ka mpeng, lets'ollo, bohloko ba ka mpeng, dyspepsia, hangata - seso sa ka mpeng le seso sa duodenal, gastritis, ho hlatsa, ho nyekeloa, ho nyekoa ke pelo, hangata, - ho hema ka mpeng, hangata haholo - gastrointestinal le hemorrhages e bolaeang, pancreatitis, colitis (haholo-holo olcerative kapa lymphocytic), stomatitis.

Ho tsoa ho sistimi ea hepatobiliary: ka seoelo - ho hloleha ha sebete haholo, hepatitis, litholoana tse sa tloaelehang tsa matšoao a tšebetso ea sebete.

Karolong ea letlalo le lisele tse poteletseng: hangata - - hemorrhage e sa sebetseng, hangata - rash, ho hlohlona, ​​methapo ea methapo ea methapo (hemorrhage), hangata - - bulous dermatitis (lefutso le kotsi la penermal, tlhahlobo ea Stevens-Johnson, erythema multiforme), angioedema , urticaria, lithethefatsi tse ling hypersensitivity syndrome, lekhopho la lithethefatsi le eosinophilia le lits'oaetso tsa kemiso (lefu la DRESS), eczema, lichen planus.

Ho tsoa ho tsamaiso ea musculoskeletal: ka seoelo - masculoskeletal hemorrhage (hemarthrosis), ramatiki, arthralgia, myalgia.

Ho tloha liphio le tsamaiso ea moroto: hangata - hematuria, ka seoelo - glomerulonephritis, e leng eona e ileng ea eketseha ka leinong maling.

Boemo bo akaretsang le karabelo setsing sa ente: khafetsa - ho tsoa mali setsing sa ente, ka seoelo - feberu.

Lithuto tsa laboratori: ka seoelo - nako e telele ea ho tsoa mali, ho fokotseha hoa palo ea neutrophils le liplatelete.

TLHOKOMELISO LITLHAKISO

ho tsoa mali le maemo a amanang le ho holofala. Haeba matšoao a ho tsoa mali a hlokometsoe nakong ea ts'ebeliso ea moriana, tlhahlobo e kholo ea mali le / kapa liteko tse ling tse nepahetseng li lokela ho etsoa hang-hang. Joalo ka li-antiplatelet agents tse ling, clopidogrel e lokela ho sebelisoa ka hloko ho bakuli ba nang le kotsi e eketsehang ea ho tsoa mali ka lebaka la ho sithabela maikutlo, ho buuoa kapa maemo a mang a methapo, hammoho le maemong a bakuli ba sebelisang acetylsalicylic acid, heparin, IIb / IIIa glycoprotein inhibitors kapa NSAIDs, haholo COX-inhibitors 2 kapa li-serotonin tse khethollang li-inhibitors tse khethiloeng (SSRIs). Hoa hlokahala ho hlokomela ka hloko lipontšo tsa matšoao a ho tsoa mali ho bakuli, ho kenyelletsa ho tsoa mali ho patehileng, haholo-holo libekeng tsa pele tsa kalafo le / kapa ka mor'a lits'ebetso tse hlaselang pelong le ts'ebetsong ea ho buuoa.Tšebeliso e tšoanang ea clopidogrel e nang le li-anticoagulants tsa molomo ha e khothalletsoe, kaha sena se ka eketsa matla a tsoang mali.

Tabeng ea ts'ebetso e reriloeng ea ts'ebetso ea bongaka e sa hlokeng tšebeliso ea li-antiplatelet agents, kalafo e nang le clopidogrel e lokela ho khaotsa matsatsi a 7 pele ho buuoa. Bakuli ba lokela ho tsebisa lingaka, ho kenyelletsa le lingaka tsa meno, hore ba nka Clopidogrel, pele ngaka e buoa kapa ha e sebelisa moriana o mocha. Clopidogrel e eketsa nako ea ho tsoa mali, ka hona e lokela ho sebelisoa ka hloko ho bakuli ba nang le menyetla ea ho tsoa mali (haholo-holo gastrointestinal le intraocular).

Bakuli ba lokela ho lemosoa hore nakong ea kalafo ka clopidogrel (a le mong kapa e kopane le acetylsalicylic acid), ho tsoa mali ho ka emisa kamora nako e tloaelehileng, le hore ba lokela ho tsebisa ngaka ka nyeoe e 'ngoe le e' ngoe ea ho tsoa mali ka mokhoa o sa tloaelehang (sebakeng kapa nako).

Thrombotic thrombocytopenic purpura. Litaba tsa thrombotic thrombocytopenic purpura (TTP) ha li fumanoe seoelo haholo kamora ts'ebeliso ea clopidogrel, ka linako tse ling esita le ka mor'a tšebeliso ea eona ea nakoana. TTP e bonts'oa ke "anemia" ea "thrombocytopenia" le "hemangi" (hemangi). TTP ke boemo bo ka bolaeang, ka hona e hloka kalafo ea kapele, ho kenyeletsoa plasmapheresis.

Haemophilia e fumanehang Nts'etsopele ea hemophilia e fumanoeng kamora ts'ebeliso ea Clopidogrel e tlalehiloe. Ha ho netefatsa ho eketseha ha nako e arotsoeng e arotsoeng ea karolo e itseng ea thromboplastin (APTT) ka kapa ho sena madi, nts'etsopele ea hemophilia e fumanoeng e lokela ho belaelloa. Bakuli ba joalo ba lokela ho khaotsa ho sebelisa Clopidogrel mme ba buisane le setsebi ho fumana kalafo e loketseng.

Haufinyane tjena o ile a tšoaroa ke lefu la ischemic. Ka lebaka la data e sa lekaneng, ha ho kgothaletswe ho fana ka Clopidogrel matsatsing a 7 a pele ka mor'a ho otloa habohloko ke ischemic.

Cytochrome P450 2C19 (CYP 2C19). Pharmacogenetics. Ho bakuli ba nang le liphatsa tsa lefutso tse fokotsang liphatsa tsa lefutso tsa CYP 2C19, ho bonoa karolo e fokolang ea metabolite ea clopidogrel ka plasma ea mali le phello e sa boleloang ea antiplatelet. Ho na le liteko tse ka khethollang mofuta oa CYP 2C19 genotype ho mokuli.

Kaha clopidogrel e fetotsoe ho metabolite ea eona e sebetsang ka mokhoa o itseng ke ts'ebetso ea CYP 2C19, ts'ebeliso ea lithethefatsi tse fokotsang ts'ebetso ea enzyme ena e kanna ea lebisa ho fokotseha ha khatello ea metabolite ea Clopidogrel e sebetsang ka plasma ea mali. Leha ho le joalo, bohlokoa ba bongaka ba tšebelisano ena ha bo hlakisoe. Ka hona, joalo ka mokhoa oa thibelo, ts'ebeliso ea nako e tšoanang ea li-inhibitors tse matla tsa CYP 2C19 li lokela ho qojoa (bona LITLHAKISO).

Ho sebelisana ha lintho ka tsela ea tlhaho. Bakuli ba lokela ho hlahlojoa bakeng sa nalane ea hypersensitivity ho li-thienopyridine tse ling (tse kang ticlopidine, prasugrel), kaha ho bile le litlaleho tsa tšebelisano lipakeng tsa thienopyridines (bona LITLHAKISO TSE KHOLO).

Li-Thienopyridine li ka etsa hore ho be le lintho tse etsahalang hantle ka linako tse ling tse kang angioedema, rash, hematological cross-reaction (thrombocytopenia, neutropenia).

Bakuli ba nang le phallo ea allergic le / kapa hematologic ha ba sebelisa moriana o tsoang sehlopheng sa thienopyridine ba ka ba le kotsi e eketsehileng ea karabelo tse tšoanang ha ba sebelisa thienopyridine e ngoe. Ka hona, bakuli ba joalo ba lokela ho shebelloa ka hloko.

Lihlopheng tse khethehileng tsa bakuli. Phihlelo ea kalafo le clopidogrel ho bakuli ba nang le bothata ba ho phekoloa ka methapo e lekanyelitsoe, ka hona, bakuli ba joalo ba lokela ho fuoa meriana ka hloko (bonaTLHOKOMELISO).

Phihlelo ea ho sebelisa lithethefatsi ho bakuli ba nang le mafu a leka-lekaneng a sebete le monyetla oa hemorrhagic diathesis li lekanyelitsoe. Ka hona, Clopidogrel e lokela ho fuoa bakuli ba joalo ka tlhokomeliso (bona APPLICATION).

Bahlomphehi. Clopidogrel-Teva e na le lactose. Bakuli ba nang le mafu a sa tloaelehang a futsitsoeng a kang ho hloka mamello galactose, khaello ea Lapp lactase kapa malabsorption ea glucose-galactose e sa sebetseng ha baa lokela ho nka meriana ena.

Boitlhokomelo bo ikhethileng ba ho lahla litšila. Masalla a sa sebelisoeng a lithethefatsi kapa litšila a lokela ho lahloa ho latela melao ea lehae.

Sebelisa nakong ea bokhachane le pelehi. Ka lebaka la khaello ea tlhaiso-leseling ea bongaka, tšebeliso ea clopidogrel nakong ea kemolo ha e batlehe ho basali ba baimana (litekanyetso).

Lithuto tsa liphoofolo ha lia ka tsa senola litlamorao tse sa tobang kapa tse sa tobang ho ima, ho emola / ho hlaha, ho beleha le ho holisa kamorao ho pelehi.

Ha ho tsejoe hore na Clopidogrel e epiloe lebeseng la matsoele. Boithuto ba liphoofolo bo bontšitse hore Clopidogrel e fetela lebese la matsoele, ka hona, ho anyesa ho lokela ho emisoa nakong ea kalafo ka clopidogrel.

Melemo. Liteko tsa liphoofolo tse sebelisang maoatleng ha li hlahise phello e mpe ea Clopidogrel ho tsoala.

Bana. Clopidogrel-Teva ha e fuoe bana.

Bokhoni ba ho susumetsa sekhahla sa karabelo ha u khanna makoloi kapa mekhoa e meng. Clopidogrel ha e ame kapa e na le phello e nyane ho bokhoni ba ho khanna makoloi kapa mekhoa e meng.

TLHOKOMELISO

anticoagulants ea molomo. Ts'ebeliso e ts'oanang ea Clopidogrel e nang le li-anticoagulants tsa molomo ha e khothalletsoe, kaha motsoako o joalo o ka eketsa matla a tsoang mali. Le ha tšebeliso ea Clopidogrel ka tekanyo ea 75 mg / ka letsatsi ha e fetole boemo ba boemo ba pharmacokinetic ba S-warfarin kapa tekanyetso e tloaelehileng ea machabeng (INR) ho bakuli ba kileng ba phekoloa ka warfarin nako e telele, tšebeliso e tšoanang ea Clopidogrel le warfarin e eketsa kotsi ea ho tsoa mali ka lebaka la boipuso. litlamorao ho heestasis.

Glycoprotein IIb / IIIa inhibitors. Clopidogrel e lokela ho sebelisoa ka hloko ho bakuli ba nang le menyetla e eketsehileng ea ho tsoa mali ka lebaka la ho sithabela maikutlo, ho buuoa kapa maemo a mang a methapo eo li-inhibitors tsa IIb / IIIa glycoprotein receptor li sebelisoang ka nako e le ngoe.

Acetylsalicylic acid. Acetylsalicylic asiti ha e fetole phello ea ha e sa kopane le "" "" "polopidogrel" - empa "Clopidogrel" e ntlafatsa phello ea acetylsalicylic acid e tsoang liphatlalatsong tsa methapo. Leha ho le joalo, tšebeliso e tšoanang ea 500 mg ea acetylsalicylic acid makhetlo a 2 ka letsatsi bakeng sa letsatsi la 1 ha ea ka ea baka keketseho e kholo ea nako ea ho tsoa mali, ea nako e telele ka lebaka la clopidogrel. Kaha tšebelisano ea pharmacodynamic pakeng tsa clopidogrel le acetylsalicylic acid e ka etsahala ka kotsi e eketsehileng ea ho tsoa mali, ts'ebeliso e tšoanang ea meriana ena e hloka tlhokomeliso. Ntle le sena, ho na le boiphihlelo ba ho nka clopidogrel le acetylsalicylic acid hammoho ho fihlela selemo.

Heparin. Ho tlalehiloe hore Clopidogrel ha e hloke phetoho ea li-heparin mme ha e ame phello ea heparin ho coagulation. Tšebeliso e tšoanang ea heparin ha ea ka ea fetola phello ea inhibitory ea clopidogrel ho kopaneng ea platelet. Kaha tšebelisano ea pharmacodynamic pakeng tsa clopidogrel le heparin e ka etsahala ka kotsi e eketsehang ea ho tsoa mali, ts'ebeliso e tšoanang ea meriana ena e hloka tlhokomeliso.

Manonyeletso a matla.Tšireletseho ea ts'ebeliso e ts'oanang ea li-clopidogrel, li-maalum tsa fibrin-itseng kapa li-fibrin tse ikhethang tsa hempin e ithutile ho bakuli ba nang le infarction e mpe ea myocardial. Khafetsa khafetsa ea phallo ea mali e ikhethang e ne e tšoana le e fumanoeng ka nako e le 'ngoe ea lithethefatsi tsa thrombolytic le heparin e nang le acetylsalicylic acid.

NSAIDs. Ts'ebeliso e kopaneng ea "Clopidogrel" le "naproxen" e tlalehiloe e eketsa palo ea mali a tsoang ka mpeng. Leha ho le joalo, ka lebaka la khaello ea lithuto mabapi le tšebelisano ea lithethefatsi le li-NSAIDs tse ling, ha e e-so tsejoe hore na menyetla ea ho tsoa mali ka mpeng e eketseha ha e sebelisoa le NSAIDs tsohle. Ka hona, ho hlokahala tlhokomeliso ha u sebelisa li-NSAIDs, haholo COX-2 inhibitors, e nang le clopidogrel.

Khetho ea Serotonin Reuptake Inhibitors (SSRIs). Kaha o na le 'nete ea hore li-SSRIs li ama ts'ebetso ea liplatelete le ho eketsa kotsi ea ho tsoa mali, ts'ebeliso e tšoanang ea li-SSRIs tse nang le clopidogrel e hloka tlhokomeliso.

Ho kopanya le meriana e meng. Kaha clopidogrel e fetotsoe ho metabolite ea eona e sebetsang ka mokhoa o itseng ke ts'ebetso ea CYP 2C19, ts'ebeliso ea lithethefatsi tse fokotsang ts'ebetso ea enzyme ena e kanna ea lebisa ho fokotseha ha khatello ea metabolite ea Clopidogrel e sebetsang ka plasma ea mali. Bohlokoa ba ts'ebelisano ena ha bo hlakisoe. Ka hona, joalo ka ts'ebetso ea thibelo, ts'ebeliso ea nako e tšoanang ea li-inhibitors tse matla tsa CYP 2C19 e lokela ho qojoa.

Lithethefatsi tse thibelang ts'ebetso ea CYP 2C19 li kenyelletsa omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxacarbazepine le chloramphenicol.

Proton inhibitors. Khokahano ea metabolite e sebetsang maling e fokotsehile ka tšebeliso ea nako e le 'ngoe kapa nako ea lihora tse 12 pakeng tsa tekanyetso ea clopidogrel le omeprazole ka tekanyo ea 80 mg. Ho fokotseha hona ho ne ho tsamaisana le ho fokotseha ha khatello ea liplatelete. Esomeprazole e lebelletsoe ho kenella ts'ebelisanong e ts'oanang le Clopidogrel.

Ho fokotseha ho sa boleloang ka tlase ha khatello ea metabolite maling ho ile ha hlokomeloa ka pantoprazole kapa lansoprazole.

Tšebelisano-hloko ea bohlokoa ea pharmacodynamic ka tšebeliso ea Clopidogrel ka nako e le ngoe le atenolol, nifedipine, kapa ka lithethefatsi tsena ka bobeli ha e so ka e bonoa. Ntle le moo, ts'ebetso ea pharmacodynamic ea Clopidogrel e lula e sa fetohe ha e ntse e sebelisa phenobarbital le estrogen.

Litlamorao tsa digoxin kapa theophylline ha lia ka tsa fetoha ha ho sebelisoa Clopidogrel.

Li-antacid ha lia ka tsa ama boemo ba ho monngoa ha Clopidogrel.

Katleho ea ketso ea antithrombotic ea clopidogrel e ka fokotsoa ke halofo ha e kopantsoe le proton pump inhibitors. Maemong ana, ho se lumellane ho tsamaiso ea nako ha ho ame ho fokotseha ha katleho ea ts'ebetso ea clopidogrel. Ho kopantsoe ha clopidogrel le proton pump inhibitors ha ho khothalletsoe.

Carboxylic clopidogrel metabolites e ka thibela ts'ebetso ea cytochrome P450 2C9. Sena se ka eketsa litekanyetso tsa plasma tsa lithethefatsi tse kang phenytoin le tolbutamide, le tse ling tse entsoe ka metaboliki e sebelisa cytochrome P450 2C9. Ntle le sena, liphetho tsa tlhahlobo ea bongaka li bontša hore phenytoin le tolbutamide li ka sebelisoa ka mokhoa o sireletsehileng ka mokhoa o ts'oanang le clopidogrel.

Ntle le tlhaiso-leseling mabapi le ho sebelisana le lithethefatsi tse ikhethang tse fanoeng kaholimo, lithuto mabapi le tšebelisano ea clopidogrel ka lithethefatsi tseo hangata li laeloang bakuli ba nang le atherothrombosis ha li e-so tšoaroe.Leha ho le joalo, bakuli ba neng ba nkile karolo lithutong tsa bongaka tsa Clopidogrel ba ile ba sebelisa lithethefatsi tse ling ka nako e le 'ngoe, ho kenyelletsa diuretics, β-adrenoreceptor blockers, li-inhibitors tsa ACE, li-antagonists tsa calcium, li-cholesterol tse theolang basebetsi, li-vasodilators tsa coronary, lithethefatsi tsa antidiabetes kalafo le GPIIb / IIIa antagonists, ntle le bopaki ba litlamorao tse bohloko tsa kliniki.

PUSELETSO

ka overdose ea clopidogrel, keketseho ea nako ea ho tsoa mali e nang le mathata a morao a ka khonehang. Ha ho tsoa mali, ho khothalletsoa kalafo ea matšoao.

Ha ho tsejoe letho ka antidote ea Clopidogrel. Haeba khafetsa ho lokisoa ha nako e telele ea ho tsoa mali ho hlokahala, phello ea Clopidogrel e ka emisoa ka ho tšeloa mali.

Litaelo tsa ho sebelisa Clopidogrel-teva

Matlapa - Letlapa le le leng:

Lintho tse sebetsang: Clopidogrel - 75 mg,

7 kapa 10 li-pcs. - lithutsoana (2, 4, 8, 9, 12) - liphutheloana tsa karete.

Kamora ho tsamaiso ea molomo ka tekanyo ea 75 mg, clopidogrel e kenngoa ka potlako ho tsoa mokokotlong oa lijo. Leha ho le joalo, khatello ea methapo ea mali e eketseha hanyane mme kamora lihora tse peli kamora ts'ebetso ha e fihle boemong bo ka khetholloang (0.025 μg / L).

Motsoako o matla maling. Metabolite ea mantlha ke ntho e sa sebetseng ea carboxylic acid mme e etsa 85% ea ntho e qalang e potoloha ka plasma. Cmax ea metabolite ena ka plasma ea mali ka mor'a litekanyetso tse ngata tsa Clopidogrel e ka ba 3 mg / l mme e bonoa hoo e ka bang hora e le 'ngoe ka mor'a tsamaiso.

The pharmacokinetics ea metabolite ea mantlha e tšoauoa ka kamano ea mola ho lethathamo la lethal dose la clopidogrel 50-150 mg.

Clopidogrel le metabolite ea mantlha li tlama liprotheine tsa plasma ka vitro (98% le 94%, ka ho latellana). Kamano ena e lula e sa khothaletsoa ka vitro ka holim'a lintho tse fapaneng.

Kamora ho kenella ha Clopidogrel e 14C e ngotsoeng, hoo e ka bang 50% ea tekanyetso e nkuoeng e qhalloa ka har'a moroto 'me e batla e le 46% ka mantle ka lihora tse 120. T1 / 2 ea metabolite e ka sehloohong ke lihora tse 8.

Ha ho bapisoa le baithaopi ba banyenyane ba phetseng hantle, pokello ea plasma ea metabolite ea mantlha e phahame haholo ho bakuli ba tsofetseng (ba lilemo li 75 le ho feta), ha ho na liphetoho lipapaling tsa nako ea mali le nako ea ho tsoa mali.

Ho mafu a matla a liphio (CC 5-15 ml / min), khatello ea "metabolite" ea mantlha ka plasma ea mali e tlase ho feta mafu a liphio a leka-lekaneng (CC 30-60 ml / min) le ho baithaopi ba phetseng hantle. Le ha litlamorao tse tlatselletsang ho kopaneng ea methapo ea methapo ea ADP li fokotsoe ha li bapisoa le tsa baithaopi ba phetseng hantle, nako ea ho tsoa mali e ile ea nyoloha ka tekanyo e tšoanang le ea baithaopi ba phetseng hantle.

Thibelo ea Plato ea Aglregation. Ka khetho e thibela ho tlama ha adenosine diphosphate (ADP) ho li-receptor tsa liplatelete le ts'ebetso ea motsoako oa GPIIb / IIIa, ka hona e thibela ho kopana ha liplatelete. E boetse e thibela pokello ea liplatelete e bakoang ke agonists tse ling ka ho thibela tšebetso e eketsehileng ea liplatelete ka ADP e lokollotsoeng. Ha e ame mosebetsi oa PDE.

Clopidogrel e fetolela li-receptor tsa ADP ka mokhoa o sa fetoheng, kahoo liplatelete li lula li sa sebetse ho pholletsa le "bophelo" ba tsona, mme ts'ebetso e tloaelehileng ea khutlisoa ha li nchafatsoa (kamora matsatsi a ka bang 7).

Matšoao a sebelisang Clopidogrel-teva

Thibelo ea mathata a ramatiki ho bakuli ba nang le myocardial infarction, ischemic stroke, kapa peripheral artery occlusion. Hammoho le acetylsalicylic acid bakeng sa thibelo ea mathata a thrombotic ho a hlobaetsang le coronary syndrome: ka karolo ea ST e phahamisitsoeng ka monyetla oa phekolo ea thrombolytic, ntle le karolo ea ST karolo (e sa tsitsang ea angina pectoris, infarction ea myocardial ntle le Q wave)ho bakuli ba tlas'a khatello ea maikutlo.

Thibelo ea mathata a ramatiki le "thromboembolic", ho kenyelletsa le stroke, le atropa ea fibrillation (atical fibrillation) boteng ba kotsi e le 'ngoe bakeng sa nts'etsopele ea mathata a methapo, ho se khone ho nka li-anticoagulants tse sa tobang le kotsi e tlase ea ho tsoa mali (hammoho le acetylsalicylic acid).

Sebelisa Clopidogrel-teva ho ima le bana

Boithuto bo lekaneng le bo laolehileng bo hlokolosi ba bongaka ba polokeho ea Clopidogrel nakong ea kemolo ha bo e so etsoe. Kopo e ka etsahala maemong a tšohanyetso feela.

Ha ho tsejoe hore na Clopidogrel e nang le lebese la matsoele e fuoe ho batho. Haeba ho hlokahala, sebelisa nakong ea lebone le lokela ho etsa qeto ea ho khaotsa ho anyesa.

Lithutong tsa liphoofolo tse sebelisitsoeng ka mokhoa oa Clopidogrel ho litekanyetso tsa 300-500 mg / kg / ka letsatsi, ha ho litlamorao le litla-morao tse mpe holima tsoalo le fetal li ile tsa fumanoa. Ho ile ha thehoa hore clopidogrel le metabolites ea eona li pepesitsoe lebeseng la matsoele.

Mofuta oa Clopidogrel Teva

Nka ka molomo 1 nako / letsatsi.

Tekanyetso ea pele le ea tlhokomelo ke 75 mg / letsatsi. Motsoako oa ho laolla ke 300 mg / ka letsatsi.

Ngoliso ea kopo e latela matšoao le boemo ba bongaka.

Clopidogrel e sebelisoa ka hloko ka kotsi e eketsehang ea ho tsoa mali ka lebaka la khatello ea maikutlo, ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso le mathata a tsamaiso ea heestasis. Ka ts'ebetso e reriloeng ea ho buoa (haeba phello ea antiplatelet e sa ratehe), clopidogrel e lokela ho emisoa matsatsi a 7 pele ho buuoa.

Clopidogrel e sebelisoa ka hloko ho bakuli ba nang le bothata ba ho kula ho matla ba hepatic, moo ho ka hlaha hemorrhagic diathesis.

Ha ho hlaha matšoao a ho tsoa mali ho hoholo (ho hlaka mali, ho ruruha, hematuria), ho bontšoa tlhahlobo ea system ea hemostatic (nako ea ho tsoa mali, palo ea liplatele, liteko tsa tšebetso ea mosebetsi oa liplatelete). Ho hlahlojoa khafetsa matšoao a laboratori ea ts'ebetso ea ts'ebetso ea sebete e kgothaletsoa.

Sebelisa ka hlokolosi ka nako e tšoanang le warfarin, heparin, NSAIDs, ka nako e telele - ka acetylsalicylic acid, hobane hajoale, polokeho ea kopo e joalo ha e so ka e qaloa.

Lithutong tsa liteko, ha ho litlamorao tsa carcinogenic le genotoxic tse fumanoeng.

Tšusumetso ho bokhoni ba ho khanna makoloi le litsamaiso tsa taolo

Kameho ea clopidogrel ho bokhoni ba ho khanna makoloi le mekhoa ea taolo ha e so thehiloe.

Bongata

Ka overdose ea clopidogrel, keketseho ea nako ea ho tsoa mali e nang le mathata a morao e ka bonoa. Ha ho tsoa mali, ho khothalletsoa kalafo ea matšoao.

Motsoako oa ketso ea clopidogrel ha o tsejoe. Haeba o hloka ho fetola hang-hang nako e telele ea ho tsoa mali, phello ea Clopidogrel e ka emisoa ka ho tšeloa mali.

Sebelisa nakong ea bokhachane kapa ka ho lactation

Ka lebaka la tlhaiso ea tlhaiso-leseling ea ts'ebeliso ea Clopidogrel nakong ea kemolo, ho ke ke ho sa ratehe ho fana ka taelo ho basali baimana.

Lithuto tsa liphoofolo ha lia ka tsa senola litlamorao tse sa tobang kapa tse sa tobang ho ima, ho emola / ho hlaha, ho beleha le ho holisa kamorao ho pelehi.

Ha ho tsejoe hore na Clopidogrel e kotsiloe lebeseng la matsoele. Liphuputso tsa liphoofolo li bontšitse hore Clopidogrel e pepesitsoe lebeseng la matsoele, ka hona, matsoele a lokela ho emisoa nakong ea kalafo ka clopidogrel.

Liteko tsa liphoofolo tse sebelisang maoatleng ha li hlahise phello e mpe ea Clopidogrel ho tsoala.

Clopidogrel-Teva ha e fuoe bana.

Likarolo tsa ts'ebeliso

Ho tsoa mali le maemo a amanang le mafu a amanang le lefu la hematological.

Haeba nakong ea ts'ebeliso ea lithethefatsi ho na le matšoao a bonts'ang monyetla oa ho tsoa mali, tlhahlobo e kholo ea mali le / kapa liteko tse ling tse nepahetseng li lokela ho etsoa hang-hang. Joalo ka lisebelisoa tse ling tsa antiplatelet, clopidogrel e lokela ho sebelisoa ka hloko ho bakuli ba nang le menyetla e eketsehileng ea ho tsoa mali ka lebaka la ho sithabela maikutlo, ho buuoa kapa maemo a mang a methapo, hammoho le ho bakuli ba sebelisang ASA, heparin, IIb / IIa glycoprotein inhibitors kapa lithethefatsi tse seng tsa anti -idalidal, haholo COX-inhibitors 2 kapa li-serotonin tsa reuptake inhibitors tse khethiloeng kapa tse 2 kapa lithethefatsi tse ling tse ka eketsang kotsi ea ho tsoa mali (e.g. pentox ifillin). Hoa hlokahala ho hlokomela ka hloko lipontšo tsa matšoao a ho tsoa mali ho bakuli, ho kenyelletsa ho tsoa mali ho patehileng, haholo-holo libekeng tsa pele tsa kalafo le / kapa ka mor'a lits'ebetso tse hlaselang pelong le ts'ebetsong ea ho buuoa. Tšebeliso e tšoanang ea clopidogrel e nang le li-anticoagulants tsa molomo ha e khothalletsoe, kaha e ka eketsa matla a tsoang mali.

Tabeng ea ts'ebetso e reriloeng ea ts'ebetso ea bongaka e hlokang ho sebelisoa, ka nakoana e hloka ts'ebeliso ea li-antiplatelet agents, kalafo e nang le clopidogrel e lokela ho khaotsa matsatsi a 7 pele ho buuoa. Bakuli ba lokela ho itlaleha ho lingaka, ho kenyelletsa lingaka tsa meno hore li ntse li nka Clopidogrel, pele u li fa lingaka tse buoang kapa pele u sebelisa moriana o mocha. Clopidogrel e eketsa nako ea ho tsoa mali, ka hona e lokela ho sebelisoa ka tlhokomeliso ho bakuli ba nang le kotsi e eketsehileng ea ho tsoa mali (haholo-holo gastrointestinal le intraocular).

Bakuli ba lokela ho lemosoa hore nakong ea kalafo ka clopidogrel (a le mong kapa e kopane le ASA), ho tsoa mali ho ka emisa kamora nako e tloaelehileng, le hore ba lokela ho tsebisa ngaka ka nyeoe e 'ngoe le e' ngoe ea ho tsoa mali ka mokhoa o sa tloaelehang (sebakeng kapa nako).

Thrombotic thrombocytopenic purpura (TTP).

Litaba tsa thrombotic thrombocytopenic purpura (TTP) ha li sa ka tsa bonoa haholo ka mor'a taolo ea clopidogrel, ka linako tse ling esita le ka mor'a tšebeliso ea eona ea nakoana. TTP e bonts'oa ke "anemia" ea "thrombocytopenia" le "hemangi" (hemangi). TTP ke boemo bo ka bolaeang, ka hona e hloka kalafo ea kapele, ho kenyeletsoa plasmapheresis.

Nts'etsopele ea hemophilia e fumanoeng kamora ts'ebeliso ea Clopidogrel e tlalehiloe. Ha ho netefatsa ho eketseha ha nako e arotsoeng e arotsoeng ea karolo e itseng ea thromboplastin (APTT) ka kapa ho sena madi, nts'etsopele ea hemophilia e fumanoeng e lokela ho belaelloa. Bakuli ba joalo ba lokela ho khaotsa ho sebelisa Clopidogrel mme ba buisane le setsebi ho fumana kalafo e loketseng.

Haufinyane tjena o ile a tšoaroa ke lefu la ischemic.

Ka lebaka la data e sa lekaneng, ha ho kgothaletswe ho fana ka Clopidogrel matsatsing a 7 a pele ka mor'a ho otloa habohloko ke ischemic.

Cytochrome P450 2C19 (CYP2C19).

Pharmacogenetics. Ho bakuli ba nang le liphatsa tsa lefutso tse fokotsang ts'ebetso ea CYP2C19, khatello e tlase ea "metabolite" ea Clopidogrel ho plasma le phello e seng e bitsitsoeng ea antiplatelet e bonoa. Ho na le liteko tse bontšang mofuta oa CYP2C19 genotype ho mokuli.

Kaha clopidogrel e fetotsoe ho metabolite ea eona e sebetsang ka mokhoa o itseng ke ts'ebetso ea CYP2C19, ts'ebeliso ea lithethefatsi tse fokotsang ts'ebetso ea enzyme ena e kanna ea lebisa ho fokotseha ha khatello ea metabolite ea Clopidogrel e sebetsang ka plasma. Leha ho le joalo, bohlokoa ba bongaka ba tšebelisano ena ha bo hlakisoe. Ka hona, joalo ka ts'ebetso ea thibelo, ts'ebeliso e ts'oanang ea li-inhibitors tse matla tsa CYP2C19 li lokela ho qojoa (bonaKarolo ea "Kamano le lihlahisoa tse ling tsa kalafo le mefuta e meng ea ts'ebelisano").

Clopidogrel e lokela ho sebelisoa ka hloko ho bakuli bao ka nako e tšoanang ba nkang lihlahisoa tseo e leng karoloana ea CYP2C8 cytochrome.

Ho sebelisana ha lintho ka tsela ea tlhaho.

Bakuli ba lokela ho hlahlojoa bakeng sa nalane ea hypersensitivity ho li-thienopyridine tse ling (tse kang ticlopidine, prasugrel), kaha ho bile le litlaleho tsa tšebelisano lipakeng tsa thienopyridines (bona karolo "Karabelo e mpe").

Li-Thienopyridine li ka etsa hore ho be le lintho tse etsahalang hantle ka linako tse ling tse kang angioedema, rash, hematological cross-reaction (thrombocytopenia, neutropenia).

Bakuli ba kileng ba ba le nalane ea karabelo ea tlhaho le / kapa ho fetoha ha hematological ha ba sebelisa lithethefatsi tse tsoang sehlopheng sa thienopyridine ba ka ba le kotsi e eketsehileng ea karabelo e tšoanang ha ba sebelisa thienopyridine. Ka hona, bakeng sa bakuli ba joalo ba lokela ho bonoa ka hloko.

Lihlopheng tse khethehileng tsa bakuli.

Phihlelo ea kalafo le clopidogrel ho bakuli ba nang ho hloleha ha rems ka hona, bakuli ba joalo ba lokela ho fuoa lithethefatsi ka hloko (sheba Karolo ea "Tekanyetso le Tsamaiso").

Boiphihlelo ba ho sebelisa lithethefatsi ho bakuli ba mafu a sebete ka tekano le monyetla oa hemorrhagic diathesis o lekantsoe. Ka hona, Clopidogrel e lokela ho fuoa bakuli ba joalo ka tlhokomeliso (bona Karolo "Karolo le Tsamaiso").

Clopidogrel-Teva e na le lactose. Bakuli ba nang le mafu a lefutso a fumanehang ka mokhoa o sa tloaelehang a kang galactose ts'oarello, khaello ea Lappase ea lactase kapa malabsorption ea glucose-galactose e sa sebetseng ha baa lokela ho nka lithethefatsi.

Mehato ea bohlokoa mabapi le ho lahla litšila

Masalla a sa sebelisoeng ke lithethefatsi kapa litšila a tlameha ho lahloa ho latela melao ea lehae.

Ho sebelisana le lithethefatsi tse ling le mefuta e meng ea litšebelisano

Lithethefatsi tse ka eketsang kotsi ea ho tsoa mali

Ho na le menyetla e eketsehileng ea ho tsoa mali ka lebaka la monyetla oa litlamorao tsa lithethefatsi. Sebelisa ka hloko meriana e meng e ka eketsang kotsi ea ho tsoa mali.

Li-anticoagulants tsa molomo. Ts'ebeliso e ts'oanang ea Clopidogrel e nang le li-anticoagulants tsa molomo ha e khothalletsoe, kaha motsoako o joalo o ka eketsa matla a tsoang mali. Leha taba ea hore tšebeliso ea clopidogrel ka tekanyo ea 75 mg ka letsatsi ha e fetole boemo ba pharmacokinetic ba S-warfarin kapa tekanyetso e tloaelehileng ea machabeng (INR) ho bakuli ba ileng ba phekoloa ka warfarin nako e telele, ts'ebeliso e tšoanang ea Clopidogrel le warfarin e eketsa kotsi ea ho tsoa mali ka lebaka la litlamorao tse ikemetseng ho heestasis.

Glycoprotein IIb Inhibitors, / IIIA . Clopidogrel e lokela ho sebelisoa ka hloko ho bakuli ba nang le menyetla e eketsehileng ea ho tsoa mali ka lebaka la ho sithabela maikutlo, ho buuoa kapa maemo a mang a methapo eo glycoprotein IIb, / IIIA inhibitors ka nako e le 'ngoe.

Acetylsalicylic acid (ASA). Acetylsalicylic acid ha e fetole phello ea ha e sa kopane le chefo ea Clopidogrel ho ADP e kentsoeng, empa Clopidogrel e ntlafatsa phello ea ASA. Leha ho le joalo, ts'ebeliso e le 'ngoe ea 500 mg ea ASA makhetlo a 2 ka letsatsi ka letsatsi le le leng ha ea ka ea baka keketseho e kholo ea nako ea ho tsoa mali, ea nako e telele ka lebaka la clopidogrel. Kaha tšebelisano ea pharmacodynamic pakeng tsa clopidogrel le acetylsalicylic acid e ka etsahala ka kotsi e eketsehileng ea ho tsoa mali, ts'ebeliso e tšoanang ea meriana ena e hloka tlhokomeliso.Ntle le sena, ho na le boiphihlelo ba ho nka clopidogrel le ASA hammoho ho fihlela selemo.

Heparin. Ho tlalehiloe hore Clopidogrel ha e hloke phetoho ea li-heparin mme ha e ame phello ea heparin ho coagulation. Tšebeliso e tšoanang ea heparin ha ea ka ea fetola phello ea inhibitory ea clopidogrel ho kopaneng ea platelet. Kaha tšebelisano ea pharmacodynamic pakeng tsa clopidogrel le heparin e ka etsahala ka kotsi e eketsehang ea ho tsoa mali, ts'ebeliso e tšoanang ea meriana ena e hloka tlhokomeliso.

Manonyeletso a matla. Tšireletseho ea tšebeliso ea nako e le 'ngoe ea li-clopidogrel, fibrin-maalum kapa fibrin e khethehileng ea li-thrombolytic le heparin li fumanoe lipatlisiso ho bakuli ba nang le infarction e mpe ea myocardial. Khafetsa ho tsoa mali ka mokhoa o ikhethang ho ne ho tšoana le ha ho sebelisoa ka nako e le 'ngoe lithethefatsi tsa thrombolytic le heparin ka ASA.

Lithethefatsi tse seng khahlanong le ho ruruha (NSAIDs). Ts'ebeliso e kopaneng ea "Clopidogrel" le "naproxen" e tlalehiloe e eketsa palo ea mali a tsoang ka mpeng. Leha ho le joalo, ka lebaka la khaello ea lithuto mabapi le tšebelisano ea lithethefatsi le li-NSAIDs tse ling, ha e e-so hlake, menyetla ea ho tsoa mali ka mpeng e eketseha ha e sebelisoa le NSAIDs tsohle. Ka hona, ho hlokahala tlhokomeliso ha u sebelisa li-NSAIDs, haholo COX-2 inhibitors, e nang le clopidogrel.

Khetho ea Serotonin Reuptake Inhibitors (SSRIs). Ka lebaka la hore li-SSRIs li ama ts'ebetso ea liplatelete le ho eketsa menyetla ea ho tsoa mali, ts'ebeliso e tšoanang ea li-SSRIs tse nang le clopidogrel e hloka tlhokomeliso.

Proton Pump Inhibitors (PPIs).

Khokahano ea metabolite e sebetsang maling e fokotsehile ka tšebeliso e le 'ngoe kapa nako ea lihora tse 12 pakeng tsa tekanyetso ea clopidogrel le omeprazole ka tekanyo ea 80 mg. Phokotso ena e ne e tsamaisana le ho fokotseha ha khatello ea liplatelete. Esomeprazole e lebelletsoe ho kenella ts'ebelisanong e ts'oanang le Clopidogrel.

Ho tlalehiloe lintlha tse ngata tse makatsang ka tšebelisanong ea pharmacodynamic / pharmacokinetic le kotsing ea pelo le pelo. Mabapi le sena, clopidogrel e nang le omeprazole kapa esomeprazole e lokela ho sebelisoa ka hloko.

Ho fokotseha ho sa boleloang ka botlalo mokokotlong oa metabolite maling ho ile ha bonoa ka pantoprazole kapa lansoprazole. Clopidogrel e ka sebelisoa le pantoprazole.

Ha ho na bopaki ba hore lithethefatsi tse ling tse fokotsang acid, tse kang proton pump blockers kapa li-antacid, li ama mosebetsi oa anti-aggregation oa clopidogrel.

Li-antacid ha li ame boemo ba ho monngoa ha Clopidogrel.

Ho kopanya le meriana e meng. Kaha clopidogrel e fetoha sebopeho sa eona se sebetsang sa metabolite ka tlase ho tšusumetso ea CYP2C19, ts'ebeliso ea lithethefatsi tse fokotsang ts'ebetso ea enzyme ena e kanna ea lebisa ho fokotseha ha khatello ea metabolite e sebetsang ea Clopidogrel ho plasma. Bohlokoa ba ts'ebelisano ena ha bo hlakisoe. Ka hona, joalo ka ts'ebetso ea thibelo, ts'ebeliso e ts'oanang ea li-inhibitors tse matla tsa CYP2C19 li lokela ho qojoa.

Litokisetso tseo e leng li-inhibitors tse matla kapa tse leka-lekaneng tsa ts'ebetso ea CYP2C19 li kenyelletsa omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, carbamazepine le efavirenz.

Tšebelisano ea bohlokoa ea pharmacodynamic ha e sebelisa Clopidogrel ka nako e le ngoe le atenolol, nifedipine kapa ka lithethefatsi ka bobeli ha lia ka tsa fumanoa. Ntle le moo, ts'ebetso ea pharmacodynamic ea Clopidogrel e lula e sa fetohe ha e ntse e sebelisoa phenobarbital le estrogen .

Melemo ea Pharmacokinetic digoxin kapa theophylline ha e fetohe ka tšebeliso e tšoanang ka clopidogrel.

Carboxylic clopidogrel metabolites e ka thibela ts'ebetso ea cytochrome P450 2C9.Sena se ka eketsa litekanyetso tsa plasma ea lithethefatsi joalo ka phenytoin le tolbutamide, le tse ling tse entsoe ka tšebeliso ea cytochrome P450 2C9. Leha ho le joalo, liphetho tsa tlhahlobo ea bongaka li bontša hore phenytoin le tolbutamide e ka sebelisoa ka polokeho ka clopidogrel.

Meriana eo e leng karolo ea cytochrome CYP2C8

Ho tlalehiloe Clopidogrel ho eketsa ho pepeseha ha boiketsetso ho baithaopi ba phetseng hantle. Ts'ebeliso ea nako e tšoanang ea li-Clopidogrel le lithethefatsi tse anngoeng haholo ke CYP2C8 cytochrome (e.g. repaglinide, paclitaxel) li lokela ho etsoa ka tlhokomeliso, ka lebaka la kotsi ea ho eketsa khatello ea bona ea mali plasma.

Ntle le tlhaiso-leseling mabapi le ho sebelisana le lithethefatsi tse ikhethang tse fanoeng kaholimo, lithuto mabapi le tšebelisano ea clopidogrel ka lithethefatsi tseo hangata li laeloang bakuli ba nang le atherothrombosis ha li e-so tšoaroe. Leha ho le joalo, bakuli ba neng ba nkile karolo lithutong tsa bongaka tsa Clopidogrel ba ile ba sebelisa lithethefatsi tse ling ka nako e le 'ngoe, ho kenyelletsa diuretics, beta-blockers, ACE inhibitors, antagonists ea calcium, lithethefatsi tse fokotsang cholesterol, li-vasodilators tsa coronary, lithethefatsi tsa antidiabetes le bahanyetsi ba GPIIb / IIIa, ha ho na bopaki ba litla-morao tse bohloko tsa kliniki.