Clopidogrel teva

Pharmacological pawg

Antithrombotic cov neeg sawv cev. Antiplatelet tus neeg sawv cev. Tus lej ATX B01A C04.

Kev tiv thaiv kab mob atherothrombosis rau cov neeg laus

• hauv cov neeg mob uas tau mob myocardial infarction (kev pib kho yog ob peb hnub, tab sis tsis pub dhau 35 hnub tom qab pib), mob ischemic stroke (qhov pib kho yog 7 hnub, tab sis tsis pub dhau 6 lub hlis tom qab pib) lossis tus neeg tau kuaj pom tus kab mob peripheral arteries (puas rau cov hlab ntsha thiab atherothrombosis ntawm cov hlab ntsha ntawm qhov qis qis dua),
• nyob rau hauv cov neeg mob uas muaj mob hlab ntsha hlwb (ACS):
• nrog cov mob caj dab mob huam sai tsis muaj ST ntu kab mob siab (tsis ruaj khov angina lossis myocardial infarction tsis muaj Q yoj), suav nrog rau cov neeg mob uas tau yoo tsis ua haujlwm thaum lub sijhawm ua pa hlab ntshav hlab plawv, nrog rau cov tshuaj acetylsalicylic acid (ASA)
• nrog rau mob myocardial infarction nrog rau qib ntu ntawm ST, kom muaj kev sib xyaw nrog acetylsalicylic acid (hauv cov neeg mob tau txais cov qauv tshuaj thiab cov uas pom muaj kev kho thrombolytic).

Kev tiv thaiv ntawm atherothrombotic thiab thromboembolic cov xwm txheej hauv atrial fibrillation:

• clopidogrel nyob rau hauv kev sib xyaw nrog ASA yog qhia hauv cov neeg mob laus nrog atrial fibrillation, uas muaj tsawg kawg yog ib qho kev pheej hmoo rau kev tshwm sim ntawm vascular cov xwm txheej, nyob rau hauv uas muaj contraindications rau kev kho mob nrog vitamin K antagonists (AVK) thiab uas muaj kev pheej hmoo tsawg los ntshav, rau kev tiv thaiv atherothrombotic thiab thromboembolic cov xwm txheej. suav nrog mob stroke.

Tsuas tshuaj thiab tswj hwm

Cov neeg laus, nrog rau cov neeg laus laus. Clopidogrel raug tshuaj 75 mg rau 1 zaug nyob rau ib hnub, tsis hais noj zaub mov dab tsi.

Clopidogrel kev kho mob hauv cov neeg mob nrog ACS tsis muaj ST ntu nqa (tsis khov kho angina pectoris lossis myocardial infarction tsis muaj Q yoj ntawm ECG) pib nrog kev txhaj tshuaj ib zaug ntawm 300 mg, thiab tom qab ntawd txuas ntxiv ntawm koob tshuaj 75 mg ib hnub ib zaug (nrog rau acetylsalicylic acid (ASA) ntawm koob tshuaj ntawm 75 325 mg / hnub). Txij li thaum siv cov tshuaj ntau dua ntawm ASA ua rau muaj kev pheej hmoo los ntshav, nws raug nquahu kom tsis txhob tshaj li ib koob tshuaj acetylsalicylic acid ntawm 100 mg. Cov sijhawm zoo ntawm kev kho mob tsis tau tsim. Cov txiaj ntsig ntawm kev siv tshuaj yeeb tshuaj txog 12 lub hlis tau qhia, thiab cov txiaj ntsig siab tshaj plaws tau pom tom qab 3 lub hlis ntawm kev kho mob.

Mob muag nrog mob myocardial infarction nrog ST ntu ntu kom siab ntxiv clopidogrel yog tus kws kho mob 75 mg ib hnub ib zaug, pib siv ib zaug ntawm 300 mg rau hauv kev sib xyaw nrog ASA, nrog lossis tsis muaj tshuaj thrombolytic. Kev kho mob rau cov neeg mob uas muaj hnub nyoog tshaj li 75 xyoos pib siv tsis tau txhaj tshuaj ntawm clopidogrel. Kev sib xyaw ua ke yuav tsum tau pib sai li sai tau tom qab pib ntawm cov tsos mob thiab yuav tsum txuas mus tsawg kawg yog plaub lub lis piam. Qhov txiaj ntsig ntawm kev siv ua ke ntawm clopidogrel nrog ASA rau ntau tshaj plaub lub lis piam nrog tus kab mob no tsis tau kawm.

Rau cov neeg mob uas muaj atrial fibrillation, clopidogrel yog siv ib zaug ntawm 75 mg. Ua ke nrog clopidogrel, kev siv tshuaj ASA yuav tsum tau pib thiab txuas ntxiv (ntawm koob tshuaj 75-100 mg ib hnub).

Yog tias tsis nco qab:

• yog tias tsawg dua 12:00 tau dhau mus txij li lub sijhawm thaum tsim nyog yuav tau coj tshuaj ntxiv, tus neeg mob yuav tsum tau noj tam sim ntawd, thiab koob tshuaj ntxiv yuav tsum tau noj nyob rau lub sijhawm ib txwm,
• yog tias nws tau dhau sij hawm ntau dua 12:00, tus neeg mob yuav tsum tau txhaj tshuaj ntxiv rau lub sijhawm tsis tu ncua tab sis tsis txhob txhaj ob npaug txhawm rau txhawm rau them rov qab.

Tsis hlauv Cov. Txoj kev kho kom zoo ntawm kev siv cov tshuaj rau cov neeg mob raum tsis ua haujlwm yog txwv.

Daim siab ua haujlwm Cov. Txoj kev kho kom zoo ntawm kev siv cov tshuaj hauv cov neeg mob uas muaj mob rau daim siab thiab ua rau muaj mob ntshav tsis txaus.

Kev phiv tshuaj

Nws tau tshaj tawm tias los ntshav yog ib qho kev phiv tshuaj thiab feem ntau tshwm sim hauv thawj lub hlis ntawm kev kho mob.

Cov kev phiv tsis zoo tau muab faib rau hauv cov plab hnyuv siab raum, qhov ntau zaus ntawm lawv qhov tshwm sim tau txhais raws li hauv qab no: feem ntau (ntawm ³ 1/100 txog ≤ 1/10), tsis xws luag (los ntawm ³ 1/1000 txog ≤ 1/100), tsis tshua muaj (ntawm ³ 1/10 000 rau ≤ 1/1000), tsis tshua muaj tshwm sim (ceeb toom Sau npe yuav ua

Dosage daim ntawv

Zaj duab xis-coated ntsiav tshuaj 75 mg

Ib ntsiav tshuaj muaj

cov tshuaj nquag: clopidogrel hydrosulfate 97.857 mg,

sib npaug rau clopidogrel 75.00 mg

cov zam: lactose monohydrate (200 mesh), microcrystalline cellulose (Avicel PH 101), hydroxypropyl cellulose (Klucel LF), microcrystalline cellulose (Avicel PH 112), crospovidone (Collidon CL), hydrogenated zaub roj hom I (Sterotex-Dritex), sodium lauryl sulfate

lub plhaub muaj pes tsawg leeg: lactose monohydrate, hypromellose 15 cP, titanium dioxide (E171), polyethylene glycol 4000, hlau oxide liab (E172), hlau oxide daj (E172), indigotine (E 132, indigo carmine txhuas cov kua roj vanish FD&C xiav No. 2)

Cov ntsiav tshuaj yog cov yeeb yaj kiab-xim los ntawm lub teeb liab mus rau liab dawb, tshuaj ntsiav zoo li tus duab, cim "93" ntawm ib sab thiab "7314" ntawm ib sab.

Cov chaw muag tshuaj

Tom qab kev tswj hwm ntawm qhov ncauj, clopidogrel yog nqus tawm sai sai ntawm lub plab zom mov. Qhov nruab nrab ntshav khov ntau uas tsis hloov pauv clopidogrel (kwv yees li 2.2-2.5 ng / ml tom qab siv ib zaug ntawm 75 mg) tau nce txog 45 feeb tom qab noj tshuaj. Kev txiav txim siab tsis txaus los ntawm kev txiav txim siab txo ntawm clopidogrel metabolites yog tsawg kawg 50%.

Clopidogrel thiab nws lub ntsiab (tsis voos) circulating metabolite hauv cov ntshav tsim kev sib cuag thim rov qab nrog tib neeg cov ntshav protein (98% thiab 94%, feem). Kev khi khi tsis tau qhov uas ntau ntawm qhov ntau.

Clopidogrel yauv yuag hnyav metabolism hauv lub siab. Clopidogrel yog metabolized nyob rau hauv ob txoj kev loj: ib qho yog kho kom haum xeeb los ntawm esterases thiab ua rau hydrolysis nrog kev tsim cov tsis ua haujlwm ntawm carboxylic acid (85% ntawm cov metabolites hauv cov hlab ntsha), lwm qhov yog sib kho los ntawm ntau yam P450 cytochromes. Ua ntej, clopidogrel yog metabolized rau nruab nrab metabolite, 2-oxo-clopidogrel. Tom qab cov metabolism ntawm cov tshuaj nruab nrab ntawm 2-oxo-clopidogrel ua rau kev tsim cov khoom noj rau lub cev, cov thiol derivative ntawm clopidogrel. Cov kab mob metabolic no tau sib kho los ntawm CYP3A4, CYP2C19, CYP1A2 thiab CYP2B6. Lub nquag thiol metabolite khi sai thiab tsis yooj yim rau cov platelet receptors, yog li inhibiting platelet aggregation.

Cmax ntawm lub zog metabolite nce ntxiv 2 zaug, ob qho tib si tom qab ib zaug thauj khoom ntawm clopidogrel 300 mg, thiab tom qab noj cov tshuaj txij nkawm ntawm 75 mg rau 4 hnub. Cmax raug pom muaj kwv yees li 30-60 feeb tom qab kev tswj hwm.

Tom qab noj clopidogrel, kwv yees li 50% yog tawm hauv cov zis thiab kwv yees li 46% nrog quav hauv lub sijhawm 120 teev tom qab tshuaj xyuas. Tom qab ib qho tshuaj qhov ncauj ntawm 75 mg, tshem tawm ib nrab-lub neej ntawm clopidogrel yog kwv yees li 6 teev. Ib nrab-lub neej ntawm lub ntsiab (tsis nco qab) metabolite ncig hauv cov ntshav yog 8 teev tom qab ib zaug thiab rov ua dua.

CYP2C19 yog kev koom tes hauv kev tsim ntawm ob qho kev siv hluav taws xob thiab kev sib xyaw ua ke, thiab 2-oxo-clopidogrel. Cov tshuaj pharmacokinetics thiab antiplatelet cuam tshuam ntawm cov nquag metabolite ntawm clopidogrel sib txawv raws CYP2C19 tus qauv.

CYP2C19 * 1 allele sib raug rau cov roj ntsha uas ua haujlwm tau zoo, thaum lub CYP2C19 * 2 thiab CYP2C19 * 3 alleles tsis ua haujlwm. Alleles CYP2C19 * 2 thiab CYP2C19 * 3 tus account rau feem ntau ntawm cov alleles nrog kev txo qis hauv European (85%) thiab Neeg Esxias (99%) qeeb qeeb. Lwm cov alleles uas cuam tshuam nrog kev ncua lossis cov metabolism hauv plab tsis tshua pom muaj thiab suav nrog CYP2C19 * 4, * 5, * 6, * 7 thiab * 8. Qhov dav dav ntawm CYP2C19 alleles, uas ua rau muaj kev cuam tshuam thiab qeeb metabolism ntawm CYP2C19, nws txawv nyob ntawm haiv neeg / haiv neeg. Cov ntaub ntawv luam tawm tsawg tsawg muaj rau cov neeg Asian, uas tsis tau tso cai rau peb los ntsuas qhov tshwm sim ntawm CYP2C19 genotyping rau kev soj ntsuam cov xwm txheej tshwm sim.

Tus neeg mob nrog rau cov xwm txheej ntawm qeeb metabolizer yuav muaj ob lub alleles nrog ploj muaj nuj nqi, raws li tau piav los saum no. Qhov ntsuas ntawm qhov tsis zoo ntawm qhov qeeb CYP2C19 metabolizer yog kwv yees li 2% rau cov neeg European, 4% ntawm haiv neeg African thiab 14% ntawm haiv neeg hauv Suav. Muaj kev ntsuam xyuas los txiav txim siab rau tus neeg mob CYP2C19 caj ces.

Tsis muaj qhov sib txawv tseem ceeb hauv kev cuam tshuam nrog cov nquag metabolite thiab hauv qhov nruab nrab kev sib cais ntawm platelet aggregation (PAT) ntawm ultrafast, nrawm thiab nruab nrab metabolizers. Hauv lub cev qeeb dua qhov tsis txaus, qhov kev cuam tshuam ntawm cov metabolite nquag yog qis dua 63-71% piv nrog cov metabolizers nrawm. Tom qab siv 300 mg / 75 mg koob tshuaj rov qab, qhov txo qis hauv tshuaj antiplatelet hauv qeeb metabolizers tau pom, nrog qhov nruab nrab PAT (5 μM ADP) yog 24% (24 teev) thiab 37% (hnub 5) piv nrog 39% PAT (24 teev) ) thiab 58% (hnub 5) ntawm cov ntsuas hluav taws xob nrawm thiab 37% (24 teev) thiab 60% (hnub 5) ntawm cov tshuaj nruab nrab. Thaum cov tshuaj tiv thaiv qeeb yog nyob rau hauv 600 mg / 150 mg regimen, qhov kev sib kis ntawm cov tshuaj metabolite yog ntau dua li ntawm 300 mg / 75 mg regimen. Ntxiv rau, PAT yog 32% (24 teev) thiab 61% (hnub 5), uas yog ntau dua li ntawm cov ntsuas qeeb qeeb uas tau nyob rau ntawm 300 mg / 75 mg regimen, tab sis zoo ib yam li lwm pawg ntawm CYP2C19 metabolizers uas nyob rau ntawm 300 mg / 75 regimen. mg Tseem tsis tau tsim txoj cai koob tshuaj rau cov neeg mob cov neeg mob no.

Tawm ntawm cov metabolite uas nquag ua haujlwm yog txo 28% hauv nruab nrab metabolizers thiab los ntawm 72% hauv cov metabolizers qeeb, thaum kev tawm tsam ntawm platelet aggregation (5 μM ADP) poob qis nrog qhov sib txawv hauv PAT ntawm 5.9% thiab 21.4%, feem, thaum piv nrog ceev kev zom zaub mov.

Cov pharmacokinetics ntawm lub cev sib nqus ntawm clopidogrel hauv cov no (nrog rau lub siab thiab lub raum ua haujlwm) cov neeg tshwj xeeb tsis paub txog.

Lub raum khiav tsis zoo

Tom qab rov qab noj dua ntawm clopidogrel ntawm 75 mg rau ib hnub hauv cov neeg mob uas lub raum mob hnyav (kev tsim kho lub peev xwm ntawm 5 mus rau 15 ml / min), kev sib cais ntawm platelet sib sau los ntawm ADP (adenosine diphosphate) tsis muaj zog (25%) dua li hauv cov kawm muaj kev noj qab haus huv, txawm li cas los xij, kev ncua sijhawm. los ntshav zoo sib xws li lub sijhawm los ntshav hauv cov ntsiab lus noj qab haus huv uas tau txais 75 mg ntawm clopidogrel ib hnub. Ib qho ntxiv, muaj kev saib xyuas zoo hauv txhua tus neeg mob.

Lub siab ua haujlwm tsis zoo

Tom qab rov qab noj tshuaj dua ntawm clopidogrel ntawm 75 mg rau ib hnub rau 10 hnub hauv cov neeg mob uas lub siab tsis ua haujlwm siab, kev txwv tsis pub platelet los ntawm ADP zoo ib yam li cov hauv kev noj qab haus huv. Qhov nruab nrab ntev ntawm lub sijhawm los ntshav hauv ob pawg kuj tseem tsis hloov.

Clopidogrel yog qhov kev qhia ua ntej rau cov tshuaj nquag, ib qho ntawm cov metabolites ntawm uas yog ib qho inhibitor ntawm platelet aggregation.Clopidogrel yog kho los ntawm CYP2C19 cov enzymes, uas ua rau muaj kev tsim cov metabolite uas tiv thaiv platelet aggregation. Cov nquag clopidogrel metabolite xaiv rau qhov cuam tshuam ntawm adenosine diphosphate (ADP) rau nws cov platelet receptor P2Y12 thiab kev ua haujlwm tom ntej ntawm GPIIb / IIIa glycoprotein complex vim ADP, thiaj li tiv thaiv platelet sib xyaw. Vim tias tsis muaj kev cuam tshuam ntawm txoj kev khi, cov platelets muaj kev puas tsuaj rau qhov seem ntawm lawv lub neej (kwv yees li 7-10 hnub), thiab cov haujlwm ib txwm ntawm platelets tau rov qab ntawm tus nqi sib haum rau lub voj voog platelet. Platelet kev sib cais tshwm sim los ntawm agonists dua li ADP kuj tseem muaj kev txwv los ntawm kev thaiv lub zog ntawm cov platelet ua haujlwm los ntawm kev kis tawm ADP.

Txij li cov nquag metabolite tsim ua siv cov CYP450 cov enzymes, qee qhov polymorphic lossis kev tsim txom los ntawm lwm cov tshuaj sib txuas, tsis yog txhua tus neeg mob muaj cov tshuaj tiv thaiv platelet txaus.

Rov qab rov qab noj dua li ntawm 75 mg rau ib hnub los ntawm thawj hnub ua rau muaj kev cuam tshuam tseem ceeb ntawm platelet sib xyaw tshwm sim los ntawm ADP. Cov nyhuv inhibitory ntxiv hnyav zuj zus ntxiv thiab nce mus txog qhov sib luag ntawm lub xeev hauv 3-7 hnub. Ntawm qhov sib npaug theem, qhov nruab nrab ntawm qhov tsis muaj kev txwv yog pom nyob rau ntawm ib koob ntawm 75 mg rau ib hnub thiab thaj tsam li ntawm 40% txog 60%. Platelet sib dhos thiab lub sijhawm ua ntshav maj mam rov qab los rau nws qib qub, feem ntau 5 hnub tom qab kho tas.

Kev tiv thaiv ntawm atherothrombotic cov xwm txheej:

- hauv cov neeg mob myocardial infarction (los ntawm ob peb hnub rau

Tsuas tshuaj thiab tswj hwm

Clopidogrel-Teva tau hais kom noj ntawm ncauj tsis hais txog kev noj zaub mov dab tsi.

Rau cov neeg laus thiab cov neeg laus laus, clopidogrel-Teva yog kho hauv ib koob tshuaj 75 mg.

Hauv cov mob plawv mob sai sai uas tsis muaj nce qib ST ntu (tsis khov kho lub hlwb lossis myocardial infarction yam tsis muaj yoj), cov tshuaj tau tawm nrog cov tshuaj thawb ib zaug ntawm 300 mg. Qhov kev saib xyuas txij nkawm yog 75 mg rau ib hnub (ua ke nrog acetylsalicylic acid ntawm ib koob ntawm 75-325 mg / hnub) rau 12 hlis. Qhov siab tshaj plaws kho tau zoo yog pom tom qab 3 lub hlis. Nws tsis raug nquahu kom dhau ib koob tshuaj acetylsalicylic acid ntau dua 100 mg, vim muaj kev pheej hmoo los ntshav.

Hauv kev mob myocardial infarction nrog kev nce ntxiv hauv ntu hauv ST, cov tshuaj tau sau rau ntawm koob tshuaj 75 mg rau ib hnub (ua ke nrog acetylsalicylic acid) pib nrog ib zaug ntawm 300 mg, nrog lossis tsis muaj tshuaj thrombolytic. Hauv cov neeg mob uas muaj hnub nyoog tshaj li 75 xyoos, Clopidogrel-Teva kev kho mob yog nqa tawm yam tsis tas siv ib qho tshuaj xwb. Kev sib xyaw ua ke yuav tsum tau pib sai li sai tau tom qab pib mob thiab pib txuas ntxiv tsawg kawg 4 lub lis piam.

Nrog atrial fibrillation, cov tshuaj tau muab tshuaj raws li ib koob ntawm 75 mg, hauv kev sib xyaw nrog acetylsalicylic acid 75-100 mg ib hnub.

Yog tias koj hla kev noj cov tshuaj tsawg dua 12 teev los ntawm cov sijhawm sib tham, tus neeg mob yuav tsum noj lub sijhawm tam sim ntawd, thiab tom qab ntawd noj cov koob tshuaj tom ntej thaum lub sijhawm teem tseg. Yog tias ntau dua 12 teev tau dhau mus lawm, tus neeg mob yuav tsum tau noj ib lub tshuaj ntawm lub sijhawm uas ib txwm tau teem tseg, yuav tsum tsis txhob noj ob zaug.

Lub raum khiav tsis zoo

Clopidogrel kev kho mob rau cov neeg mob uas lub raum lub raum tsis ua hauj lwm tsawg. Yog li ntawd, nyob rau hauv rooj plaub ntawm cov neeg mob zoo li no, cov tshuaj yuav tsum tau siv nrog ceev faj.

Lub siab ua haujlwm tsis zoo

Kev paub txog kev siv cov tshuaj rau cov neeg mob uas lub siab ua tsis taus haujlwm ntawm kev ua kom mob hnyav, nquag hemorrhagic diathesis, muaj tsawg. Hauv qhov no, hauv cov pejxeem no, cov tshuaj yuav tsum siv nrog ceev faj.

Sab sij huam

Kev los ntshav yog cov kev txhaum uas nquag pom nyob rau hauv kev kuaj mob thiab hauv lub sijhawm tom qab lub sijhawm muag, qhov uas tau sau tseg feem ntau ntawm thawj lub hlis ntawm kev kho.

Cov kev phiv tshuaj uas tau teev nyob rau hauv kev sim tshuaj los yog tshaj tawm hauv cov kev qhia tshwm sim muaj nyob rau hauv qab no.

Cov Yuav Tsum Muaj

- Hypersensitivity rau cov tshuaj nquag lossis hauv Cheebtsam ntawm cov tshuaj

- mob siab ua rau lub siab tsis ua haujlwm ntxiv

- mob ceev ceev los ntshav (mob plab kiav txhab, mob ntshav khov)

- galactose intolerance, Lapp lactase deficiency lossis glucose-galactose malabsorption tsis zoo

- cev xeeb tub thiab lactation

- cov me nyuam qis dua 18 xyoo

Cov tshuaj sib cuam tshuam

Qhov ncauj anticoagulants: kev siv clopidogrel nrog lub qhov ncauj anticoagulants tsis pom zoo, vim tias qhov kev sib xyaw no tuaj yeem nce los ntshav. Txawm hais tias noj 75 mg ntawm clopidogrel ib hnub tsis hloov pauv pharmacokinetics ntawm S-warfarin lossis thoob ntiaj teb li feem ntau piv (INR) hauv cov neeg mob noj warfarin ntev, kev siv clopidogrel thiab warfarin ua rau muaj kev pheej hmoo los ntshav vim muaj kev cuam tshuam ntawm ob qho ntawm hemostasis. cov tshuaj.

Glycoprotein IIb / IIIa inhibitors: clopidogrel yuav tsum siv nrog ceev faj hauv cov neeg mob uas tau txais IIb / IIIa glycoprotein inhibitors ib txhij.

Acetylsalicylic acid (ASA): ASA tsis hloov pauv clopidogrel-inhibition ntawm platelet aggregation ntxias los ntawm ADP, txawm li cas los xij, clopidogrel ua rau muaj txiaj ntsig ntawm ASA rau platelet aggregation ntxias los ntawm collagen. Txawm li cas los xij, kev tswj hwm tib lub sijhawm ntawm ASA ntawm 500 mg ob zaug hauv ib hnub thoob plaws hnub tsis ua rau muaj teeb meem ntau ntxiv rau lub sijhawm los ntshav vim clopidogrel. Nruab nrab ntawm clopidogrel thiab acetylsalicylic acid, kev sib txuam ntawm pharmacodynamic yog ua tau, uas ua rau muaj kev pheej hmoo ntxiv los ntshav. Yog li, kev siv ntau ntawm cov tshuaj no yuav tsum tau ua nrog ceev faj. Txawm li cas los xij, clopidogrel thiab ASA tau raug sau ua ke txog ib xyoos.

Heparin: clopidogrel tsis tas yuav hloov pauv ntawm koob tshuaj heparin lossis tsis cuam tshuam rau qhov tshwm sim ntawm heparin ntawm cov ntshav coagulation. Kev siv heparin ib txhij tsis cuam tshuam rau qhov inhibition ntawm platelet aggregation tshwm sim los ntawm clopidogrel. Nruab nrab ntawm clopidogrel thiab heparin, kev sib txuam ntawm pharmacodynamic yog ua tau, uas ua rau muaj kev pheej hmoo ntxiv los ntshav. Yog li, kev siv ntau ntawm cov tshuaj no yuav tsum tau ua nrog ceev faj.

Thrombolytic tus neeg sawv cev: kev nyab xeeb ntawm kev sib koom tes ntawm clopidogrel nrog cov fibrin-kev qhia tshwj xeeb thiab tsis muaj fibrin-tshwj xeeb rau tus neeg mob thiab heparins tau kawm hauv cov neeg mob uas muaj myocardial infarction. Qhov ntau zaus los ntshav tseem ceeb uas tseem zoo ib yam li qhov tau pom nrog kev siv cov tshuaj thrombolytic thiab heparin ua ke nrog ASA.

Nonsteroidal anti-inflammatory drugs (NSAIDs): kev sib xyaw ua ke ntawm clopidogrel thiab naproxen nce latent ntshav poob los ntawm lub plab hnyuv plab. Txawm li cas los xij, vim tias tsis muaj kev tshawb fawb txaus rau kev cuam tshuam nrog lwm tus NSAIDs, tam sim no tsis paub meej tias puas yuav muaj teeb meem rau txoj hnyuv ntshav tau tshwm sim los ntawm txhua tus NSAIDs. Yog li, kev siv NSAIDs ib txhij (suav nrog COX-2 inhibitors) thiab clopidogrel xav tau kev ceev faj.

Lwm txoj kev kho mob kom meej meej: txij li clopidogrel metabolized rau nws cov tshuaj tiv thaiv metabolite ib feem siv CYP2C19, nws cia siab tias kev siv cov tshuaj uas noj cov tshuaj tiv thaiv kev ua haujlwm ntawm cov enzyme no yuav ua rau txo qis kev siv tshuaj ntawm cov tshuaj metabolite ntawm clopidogrel. Cov kab mob tseem ceeb ntawm qhov kev sib txuam no tsis meej.Raws li kev ceev faj, kev siv ib txhij siv tshuaj uas thim CYP2C19 yuav tsum muab pov tseg.

Cov tshuaj uas noj tshuaj CYP2C19 suav nrog omeprazole thiab esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine thiab chloramphenicol.

Proton Twj Tso Kua Mis (PPIs):

Omeprazole ntawm ib koob ntawm 80 mg ib zaug ib hnub, noj ib qho nrog ib leeg nrog clopidogrel, lossis nrog 12-teev sijhawm nruab nrab ntawm ob zaug tshuaj ntawm ob lub tshuaj, txo qhov kev cuam tshuam ntawm cov metabolite nquag los ntawm 45% (thauj cov tshuaj) thiab 40% (txij nkawm tshuaj). Kev txo qis los ntawm 39% (chaw thau khoom noj) thiab 21% (txij nkawm koob tshuaj) muaj feem nrog txo qis hauv platelet aggregation txo. Esomeprazole, noj ua ke nrog clopidogrel, kuj tseem xav kom txo qis kev cuam tshuam ntawm cov tshuaj tiv thaiv metabolite. Raws li kev ceev faj, omeprazole lossis esomeprazole yuav tsum tsis txhob siv nrog clopidogrel ib txhij.

Tsawg tshaj tawm txo qis nyob rau hauv metabolite raug pom muaj nyob rau hauv cov ntaub ntawv ntawm pantoprazole thiab lansoprazole.

Plasma cov ntsiab lus ntawm cov metabolite nquag txo qis 20% (thauj cov koob tshuaj) thiab 14% (saib xyuas txij nkawm) thaum kho pantoprazole hauv ib koob 80 mg ib zaug ib hnub. Qhov no yog nrog los ntawm ib qho kev txo qis hauv nruab nrab ntawm kev txwv tsis pub platelet los ntawm 15% thiab 11%, feem. Qhov no txhais tau hais tias clopidogrel tuaj yeem siv nrog pantoprazole.

Tsis muaj pov thawj ntxiv tias lwm cov kua qaub ua rau cov tshuaj txo qis, xws li H2 receptor blockers (tshwj tsis yog cimetidine, uas yog CYP2C19 inhibitor) lossis antacids, cuam tshuam nrog cov haujlwm clopidogrel antiplatelet.

Lwm yam tshuaj:

Tsis muaj ib qho tseem ceeb ntawm cov chaw muag tshuaj sib txuas thaum noj clopidogrel nrog atenolol lossis nifedipine lossis nrog ob yam ntawm cov tshuaj yeeb dej caw no. Kev siv tib lub phenobarbital lossis estrogen kuj tsis cuam tshuam loj heev rau kev ua ub no ntawm clopidogrel.

Cov tshuaj pharmacokinetics ntawm digoxin thiab theophylline tsis hloov nrog tib lub sijhawm siv nrog clopidogrel.

Antacids tsis hloov pauv qhov degree ntawm nqus ntawm clopidogrel.

Phenytoin thiab tolbutamide, uas yog metabolized los ntawm CYP2C9, tuaj yeem siv nrog kev nyab xeeb nrog clopidogrel.

Kev tshawb nrhiav ntawm kev sib cuam tshuam ntawm clopidogrel nrog lwm cov tshuaj, feem ntau yog hais rau cov neeg mob atherothrombosis (ntxiv rau cov tshuaj uas tau tham saum toj no), tsis tau ua. Txawm li cas los xij, rau cov neeg mob koom nrog kev sim tshuaj kho mob ntawm clopidogrel leej twg coj, nrog rau clopidogrel, ntau yam tshuaj, tsis muaj kev cuam tshuam loj hauv kev kho mob. Cov tshuaj no suav nrog diuretics, beta-blockers, angiotensin-hloov enzyme inhibitors (ACE inhibitors), calcium antagonists, cov roj cholesterol ua rau cov tshuaj qis, cov tshuaj ua kom ntshav, cov tshuaj tiv thaiv kab mob (nrog rau insulin), tshuaj antiepileptic, thiab kuj yog GPII blockers. IIIa cov neeg txais.

Cov lus qhia tshwj xeeb

Los ntshav thiab mob ntshav tsis xis nyob

Vim tias txoj kev pheej hmoo ntawm los ntshav thiab hematological tsis zoo thaum kho, yog tias cov tsos mob pom zoo tias yuav los ntshav, ib qho kev kuaj ntshav dav dav thiab / lossis lwm yam kev kuaj mob uas tsim nyog yuav tsum tau ua tam sim ntawd. Zoo ib yam li lwm cov tshuaj tiv thaiv kab mob, clopidogrel yuav tsum tau siv nrog ceev faj thaum tus neeg mob uas yuav muaj kev pheej hmoo ntxiv los ntshav txuam nrog kev mob, phais mob lossis lwm yam kab mob, nrog rau cov neeg mob kho nrog ASA, heparin, IIb glycoprotein inhibitors / IIIa lossis tsis siv tshuaj steroidal anti-inflammatory tshuaj (NSAIDs), suav nrog COX-2 inhibitors. Cov neeg mob yuav tsum tau ua tib zoo saib kom pom ib qho tshwm sim ntawm los ntshav, suav nrog kev los ntshav, tshwj xeeb tshaj yog nyob rau thawj lub limtiam ntawm kev kho thiab / lossis tom qab tus txheej txheem plawv lossis phais.Kev siv ua ke ntawm clopidogrel nrog tshuaj tiv thaiv qhov ncauj tsis pom zoo, vim tias qhov no tuaj yeem nce ntshav ntau ntxiv.

Yog hais tias tus neeg mob yuav tsum tau xaiv kev phais mob, thiab cov nyhuv antiplatelet yog ib pliag tsis tsim nyog, clopidogrel yuav tsum tau tsum tsis pub dhau 7 hnub ua ntej kev phais mob. Ua ntej txhua txoj kev npaj phais mob thiab noj ib qho tshuaj tshiab, cov neeg mob yuav tsum ceeb toom cov kws kho mob thiab kws kho hniav uas lawv tau noj clopidogrel.

Clopidogrel prolongs los ntshav lub sijhawm thiab yuav tsum tau siv nrog ceev faj nyob rau hauv cov neeg mob nrog pathological hloov predisposing los ntshav (tshwj xeeb tshaj yog gastrointestinal thiab intraocular).

Cov neeg mob yuav tsum tau ceeb toom tias thaum noj Clopidogrel-Teva (ib leeg lossis hauv kev sib xyaw nrog ASA), nws yuav siv sijhawm ntev dua kom tsis txhob los ntshav, thiab tias lawv yuav tsum qhia lawv tus kws kho mob yog tias lawv tau ntsib yam tsis tau xav txog (los ntawm qhov chaw lossis sijhawm) los ntshav. Cov.

Lub Tuam Txhab Ua Yeeb Yam (Thrombocytopenic Purpura)

Tsis tshua muaj neeg coob, cov neeg muaj mob thrombocytopenic purpura (TTP) tau qhia tawm tom qab siv cov tshuaj Clopidogrel-Teva, thiab qee zaum tom qab kis tau luv luv. Nws yog tsiag ntawv los ntawm thrombocytopenia thiab microangiopathic hemolytic anemia, nrog rau kev hloov pauv hauv neurological, lub raum tsis ua haujlwm, lossis ua npaws. TTP yog lub neej muaj sia uas yuav tsum tau kho tam sim ntawd, suav nrog plasmapheresis.

Nws raug tshaj tawm tias kev noj clopidogrel ua rau kev txhim kho cov neeg muaj kabmob hemophilia. Txoj kev txhim kho tau tus mob hemophilia yuav tsum tau txiav txim siab nrog kev pom zoo nce ntxiv hauv lub sijhawm thromboplastin (APTT), nrog lossis tsis los ntshav. Kev kho mob rau cov neeg mob uas tau paub tseeb tias tau txais hemophilia thiab saib xyuas lawv tus mob yuav tsum tau nqa los ntawm cov kws tshaj lij, thiab clopidogrel yuav tsum tau tsum txiav.

Tsis ntev los no ischemic mob stroke

Vim tias tsis muaj cov ntaub ntawv, cov tshuaj tsis tuaj yeem pom zoo hauv thawj 7 hnub tom qab muaj mob stroke ischemic.

Cytochrome P450 2C19 (CYP2C19)

Pharmacogenetics: Hauv cov neeg mob uas qeeb qeeb CYP2C19 metabolizers, clopidogrel ua rau lub cev tsis tshua muaj zog ntawm cov koob tshuaj pom zoo, thiab nws muaj qhov cuam tshuam tsawg dua rau kev ua haujlwm platelet. Muaj kev ntsuam xyuas los txiav txim nyob rau hauv cov neeg mob CYP2C19 genotype.

Txij li kev tsim cov nquag clopidogrel metabolites tshwm sim, ib feem, nrog kev koom tes ntawm CYP2C19, nws cia siab tias kev siv cov tshuaj uas ua rau qhov kev txiav txim ntawm cov enzyme no yuav ua rau txo qis ntawm cov tshuaj lom neeg ntawm cov metabolites no. Cov kab mob ntsig txog qhov kev cuam tshuam no tseem tsis tau txiav txim siab. Raws li kev ceev faj, kev siv cov muaj zog lossis nruab nrab-ua yeeb yam CYP2C19 txwv tsis pub siv tib lub sijhawm nrog cov tshuaj no.

Ua xua khaub lig-ua xua

Txij li cov tshuaj tiv thaiv kab mob ua rau ua rau muaj kev fab tshuaj tau tshaj tawm ntawm thienopyridines, nws yuav tsum tau soj ntsuam seb tus neeg mob puas muaj keeb kwm kev ua kom tsis haum rau lwm cov thienopyridines, xws li ticlopidine thiab prasugrel. Hauv cov neeg mob uas muaj keeb kwm mob siab rau lwm qhov mob thienopyridines, kev saib xyuas yuav tsum tau ua tib zoo saib xyuas thaum kho cov tsos mob ntawm tus mob hypersensitivity rau clopidogrel.

Lub raum khiav tsis zoo

Clopidogrel kev kho mob rau cov neeg mob uas lub raum lub raum tsis ua hauj lwm tsawg. Yog li ntawd, nyob rau hauv rooj plaub ntawm cov neeg mob zoo li no, cov tshuaj yuav tsum tau siv nrog ceev faj.

Lub siab ua haujlwm tsis zoo

Kev paub txog kev siv cov tshuaj rau cov neeg mob uas lub siab ua tsis taus haujlwm ntawm kev ua kom mob hnyav, nquag hemorrhagic diathesis, muaj tsawg. Hauv qhov no, hauv cov pejxeem no, cov tshuaj yuav tsum siv nrog ceev faj.

Cev xeeb tub thiab lactation

Vim tias tsis muaj cov ntaub ntawv tshawb fawb txog kev cuam tshuam ntawm clopidogrel thaum cev xeeb tub, nws raug nquahu kom tsis txhob siv clopidogrel thaum cev xeeb tub los ntawm kev ceev faj.

Preclinical cov kev tshawb fawb tsis qhia txog qhov tshwm sim ncaj qha lossis tsis ncaj rau cov tshuaj rau kev xeeb tub, kev xeeb menyuam / menyuam kev loj hlob, kev yug menyuam lossis kev loj hlob tom qab yug menyuam.

Kuj tsis paub meej tias clopidogrel kis mus rau leej niam cov kua mis tau li cas. Kev tshawb fawb qhia paub tau pom tias clopidogrel kis mus rau niam mis. Raws li kev ceev faj, kev pub mis rau menyuam yuav tsum tsis txhob txuas ntxiv thaum tab tom kho nrog clopidogrel-Teva.

Kev kawm ua ntej tsis tau qhia tias clopidogrel cuam tshuam kev muaj tub ki.

Cov yam ntxwv ntawm cov nyhuv ntawm cov tshuaj ntawm lub peev xwm tsav lub tsheb lossis cov phom sij phom sij

Vim muaj qhov tshwm sim ntawm kiv taub hau lossis tsis tshua muaj kev phiv, cov tshuaj yuav tsum tau siv nrog kev ceev faj thaum tsav tsheb thiab kev siv tshuab ua haujlwm.

PHARMACOLOGICAL COV CAI

chaw muag tshuaj. Clopidogrel xaiv kev txwv ntawm txoj cai ntawm ADP rau platelet receptors thiab kev ua haujlwm ntawm glycoprotein (GP) IIb / IIIa complex thiab yog li inhibits platelet aggregation. Clopidogrel tseem inhibits platelet aggregation los ntawm lwm yam. Cov tshuaj tsis cuam tshuam rau cov kev ua ntawm PDE.

Clopidogrel irreversibly hloov platelet ADP receptors, thiab yog li ntawd cov platelets tseem tsis ua haujlwm thoob plaws hauv lub neej, thiab cov haujlwm qub ua haujlwm rov qab tom qab platelet txuas ntxiv (kwv yees 7 hnub tom qab). Cov ntsiab lus tseem ceeb thiab kev noj tshuaj-tso siab inhibition ntawm platelet aggregation tau sau tseg 2 teev tom qab kev tswj hwm qhov ncauj ntawm ib qho tshuaj clopidogrel. Kev rov ua dua ntawm kev tswj hwm ntawm ib koob ntawm 75 mg ua rau muaj kev cuam tshuam tseem ceeb ntawm platelet sib sau ua ke. Cov nyhuv intensifies zuj zus mus, thiab ib lub xeev ruaj khov yog tiav tom qab 3-7 hnub. Ntxiv mus, theem nruab nrab ntawm kev txwv tsis pub suav nrog nyob hauv qab ntawm kev nqus tshuaj ntawm 75 mg yog 40-60%. Platelet sib sau thiab lub sijhawm los ntshav rov qab los rau hauv paus pib hauv nruab nrab 7 hnub tom qab nres clopidogrel.

Cov Tshuaj Pharmacokinetics Tom qab noj ib koob tshuaj ntawm 75 mg, clopidogrel nrawm nrawm hauv lub plab zom mov. Txawm li cas los xij, nws cov kev mob siab hauv cov ntshav ntshav yog qhov tsis zoo thiab tom qab 2 teev tom qab kev tswj hwm tsis ncav cov ntsuas qhov ntsuas (0.025 μg / l).

Clopidogrel sai sai hauv daim siab. Nws lub ntsiab metabolite yog ib qho kev tsis tuaj yeem ntawm carboxylic acid thiab tso nyiaj rau kwv yees li 85% ntawm cov lus sib xyaw uas nyob rau hauv cov ntshav ntshav. C_max ntawm qhov no metabolite hauv cov ntshav ntshav tom qab rov qab noj tshuaj clopidogrel ntawm koob tshuaj 75 mg yog li 3 mg / l thiab ua tiav 1 teev tom qab kev tswj hwm.

Cov chaw muag tshuaj ntawm cov tshuaj metabolite tseem ceeb tau qhia txoj kev sib raug zoo rau hauv koob tshuaj clopidogrel 50-150 mg. Clopidogrel thiab nws lub ntsiab metabolite irreversibly khi rau cov protein plasma hauv vitro (98 thiab 94%, feem). Qhov ntawv cog lus no tseem nyob tsis ntev hauv vitro dua ntau qhov ntau.

Tom qab noj, kwv yees li 50% ntawm cov koob tshuaj tau tawm hauv cov zis thiab li 46% nrog quav hauv lub sijhawm 120 teev tom qab noj tshuaj. T_½ lub ntsiab metabolite yog 8 teev

Qhov siab ntawm cov tshuaj metabolite tseem ceeb hauv cov ntshav ntshav yog ntau dua rau cov neeg laus (ntau dua 75 xyoo) piv nrog cov tub ntxhais hluas ua haujlwm zoo. Txawm li cas los xij, ntshav siab ntau tsis yog nrog cov kev hloov hauv platelet kev sib xyaw thiab lub sijhawm ntshav. Qhov siab ntawm cov tshuaj metabolite tseem ceeb hauv cov ntshav plasma thaum noj 75 mg / hnub yog qhov qis dua rau cov neeg mob uas muaj lub raum mob hnyav (creatinine tshem tawm (CC) 5-15 ml / min) piv nrog cov neeg mob uas muaj mob raum tsawg (CC 30-60 ml / min) ) thiab cov ua haujlwm pub dawb.Txawm hais tias qhov cuam tshuam ua rau ADP-pliaj platelet aggregation txo (25%) piv nrog cov neeg ua haujlwm noj qab haus huv, lub sijhawm los ntshav tau ntev rau tib yam li cov neeg tuaj yeem noj qab haus huv uas tau txais clopidogrel ntawm koob tshuaj 75 mg / hnub.

kev tiv thaiv kev tshwm sim ntawm kev mob atherothrombosis rau cov laus:

• nyob rau hauv cov neeg mob tom qab myocardial infarction (pib kho - ob peb hnub tom qab, tab sis tsis pub dhau 35 hnub tom qab pib), ischemic stroke (pib kho - 7 hnub, tab sis tsis pub dhau 6 lub hlis tom qab pib) lossis nrog tus kab mob peripheral raug kuaj hlab ntsha (puas tsuaj rau cov hlab ntsha thiab atherothrombosis ntawm cov hlab ntsha ntawm cov qis qis),
• nyob rau hauv cov neeg mob uas muaj mob hlab ntsha hlwb (ACS):
• nrog ACS tsis tau nce S - T ntu (tsis ruaj khov angina pectoris lossis myocardial infarction tsis muaj Q nthwv dej), suav nrog rau cov neeg mob uas tau ua rau tsis haum thaum lub sijhawm cov leeg ntshav txhaws, nrog rau cov acetylsalicylic acid,
• nrog rau mob myocardial infarction nrog rau kev nce siab ntawm S - T ntu, hauv kev sib xyaw nrog acetylsalicylic acid (hauv cov neeg mob tau txais cov qauv tshuaj thiab cov uas tau pom kev kho thrombolytic).

Kev tiv thaiv ntawm atherothrombotic thiab thromboembolic cov xwm txheej nrog atrial fibrillation: clopidogrel hauv kev sib xyaw nrog acetylsalicylic acid yog qhia rau cov neeg mob laus nrog atrial fibrillation, uas muaj tsawg kawg yog ib qho kev pheej hmoo rau qhov tshwm sim ntawm vascular cov xwm txheej, contraindications rau kev kho mob nrog ntshav K antagonists, thiab muaj kev pheej hmoo tsawg ntawm prophylaxis nrog cov hlab ntsha thiab ntshav tiv thaiv. thiab thromboembolic cov xwm txheej, suav nrog mob stroke.

DAIM NTAWV THOV

cov laus, suav nrog cov neeg laus laus. Clopidogrel raug tshuaj 75 mg rau 1 zaug nyob rau ib hnub, tsis hais noj zaub mov dab tsi.

Clopidogrel kev kho mob ntawm cov neeg mob ACS tsis tau nce qib S - T ntu (tsis txaus siab angina pectoris lossis myocardial infarction tsis muaj Q yoj ntawm ECG) pib nrog ib zaug thau tawm ntawm 300 mg, thiab tom qab ntawd txuas ntxiv ntawm koob tshuaj 75 mg ib hnub ib zaug (nrog rau acetylsalicylic acid ntawm ib koob ntawm 75– 325 mg / hnub). Txij li thaum siv ntau dua ntawm cov tshuaj acetylsalicylic acid ua rau muaj kev pheej hmoo los ntshav, nws raug nquahu kom tsis txhob tshaj li 100 mg. Cov sijhawm zoo ntawm kev kho mob tsis tau tsim. Cov txiaj ntsig ntawm kev siv yeeb tshuaj mus txog 12 lub hlis tau qhia, thiab cov txiaj ntsig siab tshaj plaws tau tiav tom qab 3 lub hlis ntawm kev kho mob.

Rau cov neeg mob uas muaj tus kab mob myocardial infarction nrog rau qhov nce siab ntawm S - T ntu, clopidogrel yog tus kws kho mob 75 mg ib hnub ib zaug, pib siv ib zaug ntawm 300 mg rau hauv kev sib xyaw nrog acetylsalicylic acid, nrog lossis tsis muaj tshuaj thrombolytic. Kev kho mob rau cov neeg mob uas muaj hnub nyoog tshaj li 75 xyoos pib siv tsis tau txhaj tshuaj ntawm clopidogrel. Kev sib xyaw ua ke yuav tsum tau pib sai li sai tau tom qab pib ntawm cov tsos mob thiab yuav tsum txuas mus tsawg kawg yog 4 lub lis piam. Qhov txiaj ntsig ntawm kev siv ua ke ntawm clopidogrel nrog acetylsalicylic acid rau ntau tshaj 4 lub lis piam tsis tau kawm txog tus kab mob no.

Hauv cov neeg mob uas muaj atrial fibrillation, clopidogrel yog siv ib zaug ntawm 75 mg. Ua ke nrog clopidogrel, kev siv cov tshuaj acetylsalicylic acid yuav tsum tau pib thiab txuas ntxiv (ntawm koob tshuaj 75-100 mg / hnub).

Yog tias tsis nco qab:

• yog tias tsawg dua 12 teev tau dhau los ntawm lub sijhawm thaum nws tsim nyog yuav tau txais koob tshuaj ntxiv, tus neeg mob yuav tsum tau noj tam sim ntawd, thiab cov koob tshuaj ntxiv yuav tsum noj thaum lub sijhawm,
• yog tias ntau dua 12 teev tau dhau mus lawm, tus neeg mob yuav tsum tau txhaj dua lwm lub sijhawm tom qab ib txwm, tab sis tsis txhob muab ob npaug koob txhawm rau txhawm rau los them rov qab.

Tsis hlauv. Txoj kev kho kom zoo nrog cov tshuaj hauv cov neeg mob raum tsis ua hauj lwm.

Daim siab ua haujlwm. Txoj kev kho kom zoo ntawm kev siv tshuaj rau cov neeg mob uas muaj kab mob hauv lub siab thiab kev pheej hmoo hemorrhagic diathesis tsuas yog muaj tsawg.

SAB EFFECTS

los ntshav tau tshaj tawm tias yog ib qho kev phiv tshuaj thiab feem ntau tshwm sim hauv thawj lub hlis ntawm kev kho mob.

Cov kev phiv tsis zoo tau muab faib rau hauv cov plab hnyuv siab raum, qhov ntau zaus ntawm lawv qhov tshwm sim tau txhais raws li hauv qab no: feem ntau (los ntawm ≥1 / 100 txog ≤1 / 10), tsis xws luag (los ntawm ≥1 / 1000 txog ≤1 / 100), tsis tshua muaj (ntawm ≥1 / 10,000 txog ≤ 1/1000), tsis tshua muaj tshwm sim (los ntawm lub tshuab ua kom lub plab thiab lymphatic: tsis tshua muaj - thrombocytopenia, leukopenia, eosinophilia, neutropenia, suav nrog neutropenia, tsis tshua muaj mob - thrombotic thrombocytopenic purpura, aplastic anemia, pancytopenia, agranulocytosis, agranulocytosis, mob hnyav Cov.

Ntawm ib feem ntawm cov tshuaj tiv thaiv kab mob: tsis tshua muaj tshwm sim - muaj mob hnyav, anaphylactoid tshua, tsis paub - hla ntawm qhov tsis haum ntawm thienopyridines (xws li ticlopidine, prasugrel) (saib TSHUAJ TSHWJ XEEB).

Los ntawm psyche: tsis tshua muaj - hallucinations, tsis meej pem.

Los ntawm cov hlab ntsha hauv lub cev: tsis tshua muaj tshwm sim - intracranial los ntshav (qee qhov mob, tuag taus), mob taub hau, mob caj dab, kiv taub hau, tsis tshua muaj sia - muaj kev hloov pauv hauv saj.

Los ntawm ob sab ntawm cov khoom hauv nruab nrog ntawm lub zeem muag: ntuag dhau los - los ntshav hauv thaj tsam ntawm qhov muag (pom pob txha, mob pob txha, rov qab).

Ntawm ib feem ntawm cov khoom hnov: tsis tshua muaj - kiv taub hau.

Los ntawm cov hlab ntsha: feem ntau - hematoma, tsis tshua muaj tshwm sim - hemorrhage tseem ceeb, los ntshav los ntawm qhov mob phais, vasculitis, hlab ntsha hypotension.

Los ntawm cov kab mob ua pa: feem ntau - txhaws ntswg, tsis tshua muaj heev - los ntshav hauv txoj hlab pa (hemoptysis, mob ntsws), bronchospasm, interstitial pneumonitis, eosinophilic mob ntsws.

Los ntawm cov txheej txheem plab zom mov: feem ntau - mob plab zom mov los ntshav, zawv plab, mob plab, mob plab, ua tsis taus pa - mob plab thiab mob plab duodenal, mob plab, ntuav, xeev siab, cem quav, mob plab, tsis tshua mob heev - retroperitoneal hemorrhage, tsis tshua muaj - plab hnyuv thiab ua kom mob ntshav qab los ntshav, mob ua paug, mob caj pas, mob plab (tshwj xeeb ua mob rau daim tawv nqaij los yog mob lymphocytic), mob plab.

Los ntawm cov kab mob hepatobiliary: tsis tshua muaj tshwm sim - mob siab ua haujlwm, kab mob siab, ua haujlwm tsis txaus siab ntawm daim siab kev ua haujlwm.

Nyob rau ib feem ntawm daim tawv nqaij thiab cov nqaij mos subcutaneous: feem ntau - subcutaneous hemorrhage, tsis tshua muaj - tawm pob, khaus, intradermal hemorrhage (purpura), tsis tshua muaj tshwm sim - kev ua mob rau daim tawv nqaij (mob ua paug rau hauv lub cev, Stevens-Johnson syndrome, erythema multiforme), angioedema, cutaneous lossis exfoliative , urticaria, tshuaj tiv thaiv hypersensitivity syndrome, pob khaus yeeb tshuaj nrog eosinophilia thiab cov kev qhia ua mob (DRESS syndrome), eczema, lichen planus.

Los ntawm cov leeg musculoskeletal: tsis tshua muaj heev - musculoskeletal hemorrhage (hemarthrosis), mob caj dab, mob pob txha, mob myalgia.

Los ntawm ob lub raum thiab lub chaw tso zis: tsis tu ncua - hematuria, tsis tshua muaj tshwm sim - glomerulonephritis, muaj cov creatinine ntau ntxiv hauv cov ntshav.

Cov xwm txheej dav dav thiab cov tshuaj tiv thaiv ntawm qhov chaw txhaj tshuaj: feem ntau - los ntshav ntawm thaj chaw txhaj tshuaj, feem ntau tsis tshua muaj - ua npaws.

Kev tshawb nrhiav hauv chaw kuaj: tsis tshua muaj - lub sijhawm ntev los ntshav, txo qis ntawm cov leeg hlwb thiab qe ntshav.

COV LUS QHIA TSHWJ XEEB

los ntshav thiab pathological mob cuam tshuam nrog hematological mob. Yog tias cov tsos mob los ntshav tau sau tseg thaum siv tshuaj, yuav tsum kuaj ntshav thiab / lossis lwm yam kev kuaj mob uas tsim nyog yuav tsum ua tam sim ntawd. Zoo ib yam li lwm cov tshuaj tiv thaiv kab mob, clopidogrel yuav tsum ua tib zoo siv rau hauv cov neeg mob uas muaj kev pheej hmoo los ntshav vim yog raug mob, phais lossis lwm yam mob, nrog rau cov neeg mob siv acetylsalicylic acid, heparin, IIb / IIIa glycoprotein inhibitors lossis NSAIDs, tshwj xeeb yog COX-inhibitors. 2 lossis xaiv serotonin reuptake inhibitors (SSRIs). Nws yog ib qho tsim nyog yuav tsum tau ua tib zoo saib kom pom tseeb tias cov tsos mob los ntshav hauv cov neeg mob, suav nrog zais zais, tshwj xeeb tshaj yog nyob rau thawj lub lim tiam ntawm kev kho thiab / lossis tom qab cov txheej txheem muaj kev cuam tshuam ntawm lub siab thiab kev phais.Kev siv ua ke nrog clopidogrel nrog tshuaj tiv thaiv qhov ncauj tsis pom zoo, vim tias qhov no tuaj yeem ua rau kom ntshav khov ntau ntxiv.

Yog tias tau npaj los ntawm kev phais mob, uas ib ntus uas tsis tas siv cov tshuaj antiplatelet, kev kho mob nrog clopidogrel yuav tsum tau txiav 7 hnub ua ntej kev phais mob. Cov neeg mob yuav tsum ceeb toom cov kws kho mob, suav nrog cov kws kho hniav, hais tias lawv siv tshuaj clopidogrel, ua ntej kho cov kev phais lawv lossis ua ntej siv cov tshuaj tshiab. Clopidogrel ncua sijhawm ntev los ntshav, yog li nws yuav tsum siv kom zoo rau cov neeg mob uas muaj kev pheej hmoo los ntshav ntau (tshwj xeeb yog plab hnyuv tws thiab mob ntshav ntawm qhov ntshav).

Cov neeg mob yuav tsum tau ceeb toom tias thaum kho clopidogrel (ib leeg los yog sib xyaw nrog acetylsalicylic acid), los ntshav yuav nres tom qab li niaj hnub, thiab tias lawv yuav tsum qhia tus kws kho mob txog txhua kis tsis txawv (hauv chaw lossis sijhawm) los ntshav.

Cov tshuaj tawv muag thiav tawv thom tawv. Cov kab mob ntawm thrombotic thrombocytopenic purpura (TTP) tau muaj kev kuaj pom tsis tshua pom tom qab kev siv clopidogrel, qee zaum txawm tias tom qab nws siv sijhawm luv. TT tshwm sim los ntawm kev mob ntsws thrombocytopenia thiab microangiopathic hemolytic anemia nrog cov leeg hlwb, lub raum tsis ua haujlwm, lossis ua npaws. TTP yog qhov mob uas tuaj yeem ua rau tuag taus, thiab yog li ntawd yuav tsum tau kho tam sim ntawd, suav nrog plasmapheresis.

Nrhiav Hemophilia. Kev txhim kho ntawm kev kis tus mob hemophilia tom qab siv cov tshuaj clopidogrel tau qhia tawm. Thaum paub tseeb tias lub sijhawm ntev ntawm cov raug rho tawm ib feem thromboplastin lub sijhawm (APTT) nrog lossis tsis los ntshav, txoj kev txhim kho ntawm cov neeg mob hemophilia yuav tsum xav. Cov neeg mob zoo li no yuav tsum tsis txhob siv cov clopidogrel thiab sab laj rau tus kws kho mob tshwj xeeb kom tau txais kev kho mob uas tsim nyog.

Nyuam qhuav raug mob ischemic mob stroke. Vim tias cov ntaub ntawv tsis txaus, nws tsis pom zoo kom sau ntawv rau clopidogrel hauv thawj 7 hnub tom qab muaj mob stroke ischemic mob.

Cytochrome P450 2C19 (CYP 2C19). Cov Tshuaj Pharmacogenetics. Cov neeg mob uas tau txo cov kev ua haujlwm ntawm CYP 2C19 muaj qis qis ntawm kev siv cov tshuaj metabolite ntawm clopidogrel hauv cov ntshav plasma thiab cov lus tsis tshua muaj kev tiv thaiv antiplatelet. Muaj kev ntsuam xyuas uas tuaj yeem txheeb xyuas tus CYP 2C19 tus caj ces ntawm tus neeg mob.

Txij li thaum clopidogrel tau hloov pauv mus rau nws cov nquag metabolite ib nrab los ntawm qhov kev nqis tes ntawm CYP 2C19, kev siv cov tshuaj uas txo qis cov kev ua haujlwm ntawm qhov enzyme no yuav ua rau txo qis ntawm cov tshuaj lom neeg ntawm cov metabolite ntawm clopidogrel hauv ntshav ntshav. Txawm li cas los xij, kev kho mob tseem ceeb ntawm qhov kev sib txuam no tsis tau elucidated. Yog li, raws li kev tiv thaiv kev tiv thaiv, kev siv tib lub sijhawm muaj zog thiab muaj zog CYP 2C19 inhibitors yuav tsum zam (saib INTERACTIONS).

Ua xua hla kev sib cuam tshuam. Cov neeg mob yuav tsum raug tshuaj xyuas txog keeb kwm ntawm kev tiv thaiv tsis haum rau lwm cov thienopyridines (xws li ticlopidine, prasugrel), vim tias muaj kev tshaj tawm qhia txog cov khaub thuas sib cuam tshuam ntawm thienopyridines (saib ADVERSE EFFECTS).

Thienopyridines tuaj yeem ua rau muaj kev tsis haum nrog kev sib hais tsis haum nyhav, xws li mob caj pas, mob pob xoo, hematological hla kev tsis haum tshuaj (thrombocytopenia, neutropenia).

Cov neeg mob uas muaj kev fab tshuaj thiab / lossis hematologic kev siv tshuaj thaum siv cov tshuaj los ntawm pawg thienopyridine yuav muaj kev pheej hmoo ntau ntxiv ntawm tib cov tshuaj tiv thaiv thaum siv lwm thienopyridines. Yog li, cov neeg mob zoo li no yuav tsum tau saib xyuas kom zoo.

Cov pab pawg neeg tshwj xeeb. Kev kho mob nrog clopidogrel hauv cov neeg mob uas lub raum tsis ua haujlwm yog txwv, yog li, cov neeg mob zoo li no yuav tsum tau muab cov tshuaj nrog ceev faj (saibDAIM NTAWV THOV).

Cov kev paub ntawm kev siv cov tshuaj nyob rau hauv cov neeg mob uas muaj mob rau daim siab mob siab thiab muaj peev xwm hemorrhagic diathesis tsuas yog muaj tsawg. Yog li, clopidogrel yuav tsum tau kho rau cov neeg mob zoo li no nrog kev ceev faj (saib APPLICATION).

Tshwjxeeb. Clopidogrel-Teva muaj lactose. Cov neeg mob uas tsis tshua muaj cov kab mob xws li galactose intolerance, Lapp lactase deficiency los yog tsis muaj teeb meem qab zib-galactose malabsorption yuav tsum tsis txhob noj cov tshuaj no.

Kev ceev faj tshwj xeeb rau cov khib nyiab pov tseg. Cov tshuaj phem lossis cov tshuaj tsis siv yuav tsum muab pov tseg raws li cov cai hauv zos.

Siv thaum cev xeeb tub thiab lactation. Vim tias tsis muaj cov ntaub ntawv soj ntsuam, kev siv clopidogrel thaum cev xeeb tub yog qhov tsis xav tau rau cov poj niam cev xeeb tub (ceev faj).

Cov kev tshawb fawb tsiaj tsis qhia txog qhov cuam tshuam ncaj qha lossis tsis ncaj rau kev xeeb tub, kev yug menyuam, menyuam kev loj hlob, kev yug menyuam thiab tom qab yug menyuam.

Kuj tsis paub meej tias clopidogrel ua rau niam mis tso. Cov kev tshawb fawb tsiaj tau pom tias clopidogrel hla mus rau niam cov kua mis, yog li ntawd, kev pub mis niam yuav tsum tau tsum tsis txhob cuam tshuam thaum kho clopidogrel.

Cuam Tshuam. Cov kev sim hauv cov tsiaj sim tsis tau qhia lub ntsiab lus tsis zoo ntawm clopidogrel ntawm kev muaj me nyuam.

Cov menyuam. Clopidogrel-Teva tsis muaj kev txwv rau cov menyuam yaus.

Lub peev xwm los cuam tshuam cov tshuaj tiv thaiv tus nqi thaum tsav tsheb lossis lwm yam txheej txheem. Clopidogrel tsis cuam tshuam lossis muaj kev cuam tshuam me ntsis rau kev muaj peev xwm tsav tsheb lossis lwm yam txheej txheem.

KEV SIB THAM

tshuaj tiv thaiv qhov ncauj. Kev siv ua ke ntawm clopidogrel nrog tshuaj tiv thaiv qhov ncauj tsis pom zoo, vim tias qhov kev sib txuam no tuaj yeem ua rau ntau ntxiv los ntshav. Txawm hais tias kev siv clopidogrel ntawm koob tshuaj 75 mg / hnub tsis hloov pauv pharmacokinetic profile ntawm S-warfarin lossis kev ua haujlwm thoob ntiaj teb (INR) hauv cov neeg mob uas tau siv tshuaj warfarin tau ntev, kev siv ib txhij ntawm clopidogrel thiab warfarin ua rau muaj kev pheej hmoo los ntshav vim muaj kev ywj pheej cuam ​​tshuam rau hemostasis.

Glycoprotein IIb / IIIa inhibitors. Clopidogrel yuav tsum siv nrog ceev faj hauv cov neeg mob uas muaj kev pheej hmoo ntxiv los ntshav vim los ntawm kev raug mob, phais lossis lwm yam kab mob pathological uas IIb / IIIa glycoprotein receptor inhibitors siv tau tib lub sijhawm.

Acetylsalicylic acid. Acetylsalicylic acid tsis hloov pauv qhov cuam tshuam ntawm clopidogrel ntawm ADP-vim platelet aggregation, tab sis clopidogrel ntxiv cov nyhuv ntawm acetylsalicylic acid rau platelet aggregation ntxias los ntawm collagen. Txawm li cas los xij, kev siv ib txhij 500 mg ntawm acetylsalicylic acid 2 zaug hauv ib hnub rau 1 hnub tsis ua rau muaj teeb meem loj ntxiv rau lub sijhawm los ntshav, lub caij nyoog ntev vim clopidogrel. Txij li thaum pharmacodynamic kev sib cuam tshuam ntawm clopidogrel thiab acetylsalicylic acid muaj peev xwm ua tau nrog kev pheej hmoo los ntshav ntau, kev siv cov tshuaj no ib zaug yuav tsum ceev faj. Dua li ntawm qhov no, muaj kev paub noj clopidogrel thiab acetylsalicylic acid ua ke mus txog ib xyoos.

Heparin. Nws tau tshaj tawm tias clopidogrel tsis xav tau koob kho ntawm heparin thiab tsis cuam tshuam rau cov nyhuv ntawm heparin ntawm kev sib tsoo. Kev siv txhij ib txhij ntawm heparin tsis hloov pauv qhov cuam tshuam ntawm clopidogrel ntawm platelet aggregation. Txij li thaum pharmacodynamic kev sib cuam tshuam ntawm clopidogrel thiab heparin muaj peev xwm ua tau nrog kev pheej hmoo los ntshav ntau, kev siv cov tshuaj no ib zaug yuav tsum ceeb toom.

Thrombolytic tus neeg sawv cev.Kev nyab xeeb ntawm kev siv tib txhij ntawm clopidogrel, fibrin-specific lossis fibrin-specific thrombolytic agents thiab heparin tau kawm hauv cov neeg mob uas muaj myocardial infarction. Qhov ntau zaus los ntshav tseem ceeb ntawm kev kuaj ntshav tau zoo ib yam li tau tshawb pom nrog kev siv cov tshuaj thrombolytic thiab heparin nrog acetylsalicylic acid.

NSAIDs. Qhov kev siv ntau tshaj plaws ntawm clopidogrel thiab naproxen tau tshaj tawm tias ua rau muaj kev mob ntsws ntau ntau los ntshav. Txawm li cas los xij, vim tias tsis muaj kev kawm txog kev sib cuam tshuam ntawm cov tshuaj nrog lwm cov NSAIDs, nws tseem tsis tau txiav txim siab tias qhov kev pheej hmoo ntawm txoj hnyuv ntshav yuav nce ntxiv thaum siv nrog txhua NSAIDs. Yog li, yuav tsum ceev faj thaum siv NSAIDs, tshwj xeeb yog COX-2 inhibitors, nrog clopidogrel.

Xaiv Serotonin Reuptake Inhibitors (SSRIs). Muab qhov tseeb tias SSRIs cuam tshuam platelet kev ua kom lub cev thiab nce ntshav tawm los ntshav, kev siv SSRIs sib xyaw nrog clopidogrel xav tau kev ceev faj.

Ua ke nrog lwm cov tshuaj. Txij li thaum clopidogrel tau hloov pauv mus rau nws cov nquag metabolite ib nrab los ntawm qhov kev nqis tes ntawm CYP 2C19, kev siv cov tshuaj uas txo cov kev ua haujlwm ntawm cov enzyme no yuav ua rau txo qis ntawm cov tshuaj lom neeg ntawm cov metabolite ntawm clopidogrel hauv ntshav ntshav. Cov kab mob tseem ceeb hauv kev cuam tshuam ntawm no tsis tau elucidated. Yog li, raws li kev tiv thaiv kev tiv thaiv, kev siv tib lub sijhawm muaj zog thiab muaj zog CYP 2C19 inhibitors yuav tsum zam.

Cov tshuaj uas thim cov kev ua si ntawm CYP 2C19 suav nrog omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxacarbazepine thiab chloramphenicol.

Proton twj tso kua mis inhibitors. Qhov kev sib zog ntawm cov tshuaj metabolite hauv cov ntshav txo qis nrog kev siv tib lub sijhawm los yog 12-teev sib nrug ntawm koob tshuaj clopidogrel thiab omeprazole hauv koob tshuaj 80 mg. Qhov kev txo qis no tau nrog los ntawm kev txo qis hauv kev txo cov platelet aggregation. Esomeprazole yuav tsum nkag mus rau hauv kev sib txuam zoo ib yam nrog clopidogrel.

Ib qhov tsawg tshaj tawm los txo qis hauv kev saib xyuas ntawm cov tshuaj metabolite hauv cov ntshav tau sau tseg nrog pantoprazole lossis lansoprazole.

Clinically tseem ceeb kev sib txuam ntawm kev sib txuam nrog kev siv clopidogrel ib txhij nrog atenolol, nifedipine, lossis nrog rau ob qho tshuaj tsis tau txheeb xyuas. Tsis tas li ntawd, pharmacodynamic kev ua haujlwm ntawm clopidogrel tseem tsis hloov pauv thaum siv phenobarbital thiab estrogen.

Qhov cuam tshuam ntawm digoxin lossis theophylline tsis hloov pauv thaum kev siv clopidogrel.

Antacids tsis cuam tshuam rau theem ntawm kev nqus ntawm clopidogrel.

Qhov ua tau zoo ntawm antithrombotic kev ua ntawm clopidogrel tuaj yeem txo los ntawm yuav luag ib nrab thaum ua ke nrog cov tshuaj tiv thaiv proton twj tso kua mis. Hauv qhov xwm txheej no, qhov tsis xws luag hauv kev tswj hwm ntawm lub sijhawm tsis cuam tshuam qhov txo qis hauv clopidogrel kev ua haujlwm. Kev sib xyaw ntawm clopidogrel nrog proton twj tso kua mis inhibitors tsis pom zoo.

Carboxylic clopidogrel metabolites tuaj yeem tiv thaiv kev ua si ntawm cytochrome P450 2C9. Qhov no tuaj yeem ua rau nce ntshav nce ntxiv ntawm cov tshuaj xws li phenytoin thiab tolbutamide, thiab lwm yam uas yog metabolized siv cytochrome P450 2C9. Dua li ntawm qhov no, qhov tshwm sim los ntawm kev kawm tshawb pom tau hais tias phenytoin thiab tolbutamide tuaj yeem siv tau nyab xeeb ib txhij nrog clopidogrel.

Tsuas yog zam ntawm cov ntaub ntawv hais txog kev cuam tshuam nrog rau cov tshuaj tshwj xeeb tau muab rau saum toj no, kev tshawb fawb txog kev cuam tshuam ntawm clopidogrel nrog cov tshuaj uas feem ntau tau muab rau cov neeg mob atherothrombosis tsis tau ua.Txawm li cas los xij, cov neeg mob uas koom nrog cov kev tshawb fawb soj ntsuam ntawm clopidogrel siv lwm yam tshuaj rau tib lub sijhawm, suav nrog diuretics, β-adrenoreceptor blockers, ACE inhibitors, calcium antagonists, cov roj ntsha ua rau cov kab mob ntshav qis, cov tshuaj tiv thaiv kab mob ntshav, tshuaj tiv thaiv kab mob (nrog rau cov tshuaj insulin), tshuaj antiepileptic, cov tshuaj hormones kev kho thiab GPIIb / IIIa cov thaiv kev ua yeeb yam, tsis muaj pov thawj ntawm cov kab mob tseem ceeb hauv kev mob loj.

OVERDOSE

nrog kev noj tshuaj ntau dua ntawm clopidogrel, kev nce ntshav hauv lub sijhawm nrog rau cov teeb meem tom ntej yog qhov ua tau. Yog tias los ntshav, kev kho mob tus yam ntxwv pom zoo.

Clopidogrel antidote tsis paub txog. Yog tias kho lub sijhawm sai sai ntawm lub sijhawm ntev los ntshav yog qhov tsim nyog, cov nyhuv ntawm clopidogrel tuaj yeem nres los ntawm kev hloov ntshav ntawm platelet pawg.

Cov lus qhia rau kev siv clopidogrel-teva

Ntsiav tshuaj - 1 ntsiav tshuaj:

Cov tshuaj kom nquag: clopidogrel - 75 mg,

7 lossis 10 pcs. - hlwv (2, 4, 8, 9, 12) - pob khoom los ntawm cardboard.

Tom qab qhov ncauj tswj hwm ntawm ib koob tshuaj 75 mg, clopidogrel nrawm nrawm los ntawm lub plab zom mov. Txawm li cas los xij, qhov siab nyob hauv ntshav ntshav nce siab me ntsis thiab tom qab 2 teev tom qab kev tswj hwm tsis ncav qib uas yuav txiav txim siab tau (0.025 μg / L).

Kev siv zog hauv lub siab. Lub ntsiab metabolite yog ib qho kev tso tawm tsis ua haujlwm ntawm carboxylic acid thiab ua rau kwv yees li 85% ntawm cov pib tshuaj sib kis hauv cov ntshav. Cmax ntawm cov metabolite no hauv cov ntshav ntshav tom qab rov qab noj tshuaj ntawm clopidogrel yog li 3 mg / l thiab raug pom muaj kwv yees li 1 teev tom qab kev tswj hwm.

Lub pharmacokinetics ntawm lub ntsiab metabolite yog tus cwj pwm ntawm kab kev sib raug zoo hauv koob tshuaj clopidogrel 50-150 mg.

Clopidogrel thiab lub ntsiab metabolite irreversibly khi rau cov protein plasma hauv vitro (98% thiab 94%, feem). Qhov kev sib raug zoo no tseem nyob tsis tau hauv vitro dhau ntawm ntau qhov ntau.

Tom qab kev noj ntawm 14C-daim ntawv lo clopidogrel, kwv yees li 50% ntawm qhov kev noj tshuaj tau tawm hauv cov zis thiab kwv yees li 46% nrog quav rau 120 teev T1 / 2 ntawm lub ntsiab metabolite yog 8 teev.

Piv nrog cov tub ntxhais hluas noj qab nyob zoo, lub plasma qhov ntau ntawm cov tshuaj metabolite tseem ceeb dua rau cov neeg mob laus (75 xyoo thiab laus dua), tsis muaj kev hloov pauv hauv platelet sib sau thiab lub sijhawm ua ntshav.

Hauv cov kab mob hauv lub raum loj (CC 5-15 ml / min), qhov tseem ceeb ntawm cov zaub mov tseem ceeb hauv cov ntshav plasma qis dua li mob raum tsawg (CC 30-60 ml / min) thiab hauv cov neeg ua haujlwm noj qab haus huv. Txawm hais tias qhov cuam tshuam ua rau ADP-hob ua platelet sib xyaw tau txo qis piv nrog cov neeg ua haujlwm noj qab haus huv zoo, lub sijhawm los ntshav ntxiv rau tib yam li cov neeg tuaj yeem noj qab haus huv.

Platelet Kev Sib Tw Ntaus. Xaiv tsis tau qhov kev khi ntawm adenosine diphosphate (ADP) rau cov platelet receptors thiab kev ua kom zoo ntawm GPIIb / IIIa complex, yog li inhibiting platelet aggregation. Nws tseem ua rau platelet sib sau ua ke los ntawm lwm tus agonists los ntawm kev thaiv cov pob txha muaj ntau ntxiv los ntawm kev tso tawm ADP. Tsis cuam tshuam dab tsi rau PDE kev ua ub no.

Clopidogrel irreversibly hloov ADP receptors ntawm platelets, yog li cov platelets tseem tsis ua haujlwm thoob lawv "lub neej", thiab kev ua haujlwm zoo li qub tau rov qab los thaum lawv rov ua dua tshiab (tom qab txog 7 hnub).

Kev taw qhia txog kev siv clopidogrel-teva

Kev tiv thaiv ntawm kev mob thrombotic hauv cov neeg mob nrog myocardial infarction, ischemic stroke, lossis peripheral artery occlusion. Ua ke nrog cov tshuaj acetylsalicylic acid rau kev tiv thaiv kev mob thim rov qab hauv kev muaj mob ntawm cov leeg mob: nrog rau ST ntu nce nrog qhov ua tau ntawm kev kho thrombolytic, tsis muaj ST ntu kev nce siab (tsis khov kho lub hlwb pectoris, myocardial infarction tsis muaj Q yoj), suav nroghauv cov neeg mob qis qis stenting.

Kev tiv thaiv ntawm kev mob ntshav thiav thiab mob plab, nrog rau mob stroke, nrog atrial fibrillation (atrial fibrillation) thaum muaj tsawg kawg ib qho kev pheej hmoo rau kev txhim kho vascular teebmeem, tsis muaj peev xwm coj anticoagulants thiab tsis tshua muaj kev pheej hmoo los ntshav (ua ke nrog acetylsalicylic acid).

Clopidogrel-teva Siv hauv cev xeeb tub thiab menyuam yaus

Cov kev txwv tsis raug thiab tswj hwm kev tshawb fawb soj ntsuam kev nyab xeeb ntawm clopidogrel thaum cev xeeb tub tsis tau ua. Kev thov yuav siv tau tsuas yog thaum muaj xwm txheej ceev.

Kuj tsis paub meej tias clopidogrel nrog leej niam cov kua mis puas nyob hauv tib neeg. Yog tias tsim nyog, siv thaum lactation yuav tsum txiav txim siab txog kev txiav kev pub niam mis.

Hauv kev sim tsiaj cov kev tshawb fawb siv clopidogrel nyob rau hauv koob tshuaj ntawm 300-500 mg / kg / hnub, tsis muaj teebmeem teratogenic thiab tsis zoo rau kev muaj menyuam thiab kev loj hlob ntawm lub plab. Nws tau tsim tsa tias clopidogrel thiab nws cov metabolites yog tawm hauv cov kua mis.

Clopidogrel Teva Dosage

Siv qhov ncauj 1 teev / hnub.

Qhov pib koob tshuaj thiab txij nkawm yog 75 mg / hnub. Qhov kev thauj khoom hnyav yog 300 mg / hnub.

Daim ntawv thov kev hwm nyob ntawm qhov ntsuas thiab qhov xwm txheej hauv tsev kho mob.

Clopidogrel siv nrog nrog ceev faj nrog kev pheej hmoo ntawm kev los ntshav vim los ntawm kev raug mob, kev phais mob, thiab kev cuam tshuam ntawm cov kab mob hemostasis. Nrog cov kev npaj phais mob (yog tias muaj cov nyhuv antiplatelet tsis tsim nyog), clopidogrel yuav tsum tau tsum txiav 7 hnub ua ntej kev phais mob.

Clopidogrel tau siv nrog ceeb toom rau cov neeg mob uas muaj kab mob siab rau lub cev hnyav, uas ua rau hemorrhagic diathesis tshwm sim.

Thaum cov tsos mob ntawm kev los ntshav ntau dhau (cov pos hniav los ntshav, menorrhagia, hematuria) tshwm sim, kev kawm txog cov kab mob hemostatic (lub sijhawm los ntshav, platelet suav, platelet ua haujlwm kev ntsuam xyuas) yog qhia. Peb nquahu kom ntsuas lub chaw kuaj ntsuas lub siab seb puas ua haujlwm lub siab.

Siv nrog ceev faj ib txhij nrog warfarin, heparin, NSAIDs, ntev - nrog acetylsalicylic acid, vim tias tam sim no, kev nyab xeeb ntawm daim ntawv thov tsis tau hais meej ua tiav.

Hauv kev sim tshuaj, tsis pom muaj cov carcinogenic thiab genotoxic cov teebmeem.

Cuam tshuam rau kev muaj peev xwm tsav tsheb thiab tswj cov tshuab

Cov nyhuv ntawm clopidogrel ntawm kev muaj peev xwm tsav tsheb thiab kev tswj cov tshuab tseem tsis tau tsim.

Noj ntau dhau

Nrog kev siv tshuaj ntau dhau ntawm clopidogrel, ib qho kev nce ntxiv hauv lub sijhawm los ntshav nrog cov teeb meem tom qab tuaj yeem pom. Yog tias los ntshav, kev kho mob tus yam ntxwv pom zoo.

Qhov tshuaj tiv thaiv ntawm kev ua ntawm clopidogrel tsis paub. Yog tias koj xav tau kho tam sim ntawd lub sijhawm los ntshav ncua ntev, cov nyhuv ntawm clopidogrel tuaj yeem nres los ntawm kev hloov ntshav ntawm platelet pawg.

Siv thaum cev xeeb tub lossis lactation

Vim tias tsis muaj cov ntaub ntawv soj ntsuam hais txog kev siv clopidogrel thaum cev xeeb tub, nws yog qhov tsis xav kom muab tshuaj rau cov poj niam cev xeeb tub (ceev faj).

Cov kev tshawb fawb tsiaj tsis qhia txog qhov cuam tshuam ncaj qha lossis tsis ncaj rau kev xeeb tub, kev yug menyuam, menyuam kev loj hlob, kev yug menyuam thiab tom qab yug menyuam.

Kuj tsis paub meej tias clopidogrel ua rau niam mis tso. Cov kev tshawb fawb tsiaj tau pom tias clopidogrel yog cov tawm hauv niam cov kua mis, yog li kev pub mis niam yuav tsum tau muab txiav tawm thaum kho clopidogrel.

Cov kev sim hauv cov tsiaj sim tsis tau qhia lub ntsiab lus tsis zoo ntawm clopidogrel ntawm kev muaj me nyuam.

Clopidogrel-Teva tsis muaj kev txwv rau cov menyuam yaus.

Daim ntawv thov nta

Kev los ntshav thiab pathological cuam tshuam nrog hematological mob.

Yog tias thaum lub sijhawm siv cov tshuaj muaj cov tsos mob qhia tias muaj peev xwm los ntshav, kev kuaj ntshav ntau thiab / lossis lwm yam kev kuaj mob tsim nyog yuav tsum tau ua tam sim ntawd. Zoo ib yam li lwm cov tshuaj tiv thaiv kab mob, clopidogrel yuav tsum tau siv nrog ceev faj hauv cov neeg mob uas muaj kev pheej hmoo los ntshav vim los ntawm kev raug mob, phais lossis lwm yam mob, nrog rau cov neeg mob siv ASA, heparin, IIb / IIa glycoprotein inhibitors lossis tshuaj tsis-steroidal anti-inflammatory tshuaj, tshwj xeeb hauv COX-inhibitors 2 lossis xaiv serotonin reuptake inhibitors (SSRIs) lossis lwm yam tshuaj uas yuav ua rau muaj kev pheej hmoo los ntshav (piv txwv li, pentox ifillin). Nws yog ib qho tsim nyog yuav tsum tau ua tib zoo saib kom pom tseeb tias cov tsos mob los ntshav hauv cov neeg mob, suav nrog zais zais, tshwj xeeb tshaj yog nyob rau thawj lub lim tiam ntawm kev kho thiab / lossis tom qab cov txheej txheem muaj kev cuam tshuam ntawm lub siab thiab kev phais. Kev siv ua ke nrog clopidogrel nrog tshuaj tiv thaiv qhov ncauj tsis pom zoo, vim tias nws tuaj yeem ua rau ntau ntxiv los ntshav.

Yog tias tau npaj los ntawm kev phais mob, ib ntus yuav tsum siv cov tshuaj antiplatelet, kev kho mob nrog clopidogrel yuav tsum tau tsum txiav 7 hnub ua ntej kev phais mob. Cov neeg mob yuav tsum ceeb toom rau kws kho mob, suav nrog cov kws kho hniav uas lawv tau noj clopidogrel, ua ntej sau ntawv kho ib qho kev phais rau lawv lossis ua ntej siv cov tshuaj tshiab. Clopidogrel ncua sijhawm ntev los ntshav, yog li nws yuav tsum tau siv nrog ceev faj hauv cov neeg mob uas muaj kev pheej hmoo los ntshav ntau (tshwj xeeb yog plab hnyuv tws thiab ntshav ntawm nplooj siab).

Cov neeg mob yuav tsum tau ceeb toom tias thaum kho tus mob clopidogrel (ib leeg lossis ua ke nrog ASA), kev los ntshav yuav tso tseg lig dua li niaj hnub, thiab tias lawv yuav tsum qhia tus kws kho mob txog txhua kis mob ntshav tsis xwm yeem (hauv qhov chaw lossis sijhawm).

Ua kom pom cov kab mob thrombocytopenic purpura (TTP).

Cov xwm txheej ntawm thrombotic thrombocytopenic purpura (TTP) tsis tshua pom muaj tom qab clopidogrel tswj hwm, qee zaum txawm tias tom qab nws siv sijhawm luv. TT tshwm sim los ntawm kev mob ntsws thrombocytopenia thiab microangiopathic hemolytic anemia nrog cov leeg hlwb, lub raum tsis ua haujlwm, lossis ua npaws. TTP yog qhov mob uas tuaj yeem ua rau tuag taus, thiab yog li ntawd yuav tsum tau kho tam sim ntawd, suav nrog plasmapheresis.

Kev txhim kho ntawm kev kis tus mob hemophilia tom qab siv cov tshuaj clopidogrel tau qhia tawm. Thaum paub tseeb tias lub sijhawm ntev ntawm cov raug rho tawm ib feem thromboplastin lub sijhawm (APTT) nrog lossis tsis los ntshav, txoj kev txhim kho ntawm cov neeg mob hemophilia yuav tsum xav tias tsam. Cov neeg mob zoo li no yuav tsum tsis txhob siv clopidogrel thiab sab laj rau tus kws kho mob tshwj xeeb kom tau txais kev kho mob uas tsim nyog.

Nyuam qhuav raug mob ischemic mob stroke.

Vim tias cov ntaub ntawv tsis txaus, nws tsis pom zoo kom sau ntawv rau clopidogrel hauv thawj 7 hnub tom qab muaj mob stroke ischemic mob.

Cytochrome P450 2C19 (CYP2C19).

Cov Tshuaj Pharmacogenetics. Hauv cov neeg mob uas tsis muaj cov caj ces txo CYP2C19, qhov qis ntawm kev siv cov khoom ua kom nquag pliag ntawm clopidogrel hauv ntshav thiab qhov tsawg dua cov nyhuv antiplatelet tau pom. Muaj kev ntsuam xyuas kom paub cov cim CYP2C19 caj hlav hauv ib tus neeg mob.

Txij li thaum clopidogrel hloov mus rau hauv nws cov nquag metabolite ib feem nyob rau hauv kev cuam tshuam ntawm CYP2C19, kev siv cov tshuaj uas txo qis cov kev ua haujlwm ntawm cov enzyme no yuav ua rau txo qis ntawm cov tshuaj lom neeg ntawm cov metabolite ntawm clopidogrel hauv ntshav. Txawm li cas los xij, kev kho mob tseem ceeb ntawm qhov kev sib txuam no tsis tau elucidated. Yog li, raws li kev tiv thaiv kev tiv thaiv, kev siv tib lub sijhawm muaj zog thiab muaj zog CYP2C19 inhibitors yuav tsum zam (saibNtu “Kev cuam tshuam nrog lwm cov khoom lag luam tshuaj thiab lwm yam kev sib cuam tshuam”).

Clopidogrel yuav tsum siv nrog ceev faj hauv cov neeg mob uas ib txhij nqa cov khoom uas yog cov txheej txheem rau CYP2C8 cytochrome.

Ua xua hla kev sib cuam tshuam.

Cov neeg mob yuav tsum raug txheeb xyuas txog keeb kwm ntawm kev tiv thaiv tsis haum rau lwm cov thienopyridines (xws li ticlopidine, prasugrel), vim tias muaj kev tshaj tawm qhia txog cov khaub thuas sib tiv thaiv ntawm thienopyridines (saib ntu “Cov kev tsis haum”).

Thienopyridines tuaj yeem ua rau muaj kev tsis haum nrog kev sib hais tsis haum nyhav, xws li mob caj pas, mob pob xoo, hematological hla kev tsis haum tshuaj (thrombocytopenia, neutropenia).

Cov neeg mob uas muaj keeb kwm kev ua xua thiab / lossis hematological tsis haum xeeb thaum siv tshuaj los ntawm pawg thienopyridine yuav muaj kev pheej hmoo ntawm cov kev tsis haum tshuaj zoo thaum siv lwm thienopyridines. Yog li ntawd, rau cov neeg mob zoo li no yuav tsum tau ua tib zoo saib xyuas.

Cov pab pawg neeg tshwj xeeb.

Kev kho kom paub nrog clopidogrel hauv cov neeg mob nrog lub raum tsis ua hauj lwm txwv, yog li ntawd, cov neeg mob zoo li no yuav tsum tau muab cov tshuaj nrog ceev faj (saib Ntu "Kev Tu thiab Tswj Xyuas").

Kev paub ntawm kev siv cov tshuaj hauv cov neeg mob nrog daim siab mob nqeeb thiab qhov tseem ceeb hemorrhagic diathesis yog txwv. Yog li no, clopidogrel yuav tsum tau kho rau cov neeg mob zoo li no nrog kev ceev faj (saib Ntu "Dosage thiab Administration").

Clopidogrel-Teva muaj lactose. Cov neeg mob uas tsis tshua muaj mob muaj keeb xws li galactose intolerance, Lapp lactase deficiency los yog cuam tshuam cov piam thaj-galactose malabsorption yuav tsum tsis txhob noj cov tshuaj no.

Cov lus ceeb toom tshwj xeeb txog kev khib nyiab pov tseg

Cov tshuaj phem lossis cov tshuaj tsis siv yuav tsum tau muab pov tseg raws li cov cai hauv zos.

Kev sib cuam tshuam nrog lwm yam tshuaj thiab lwm yam kev sib cuam tshuam

Cov tshuaj uas tuaj yeem ua rau muaj feem yuav los ntshav

Muaj kev pheej hmoo ntawm kev los ntshav yog los ntawm kev muaj peev xwm ntawm kev cuam tshuam ntawm cov tshuaj. Siv nrog ceev faj lwm cov tshuaj uas yuav ua rau muaj kev pheej hmoo los ntshav.

Qhov ncauj anticoagulants. Kev siv ua ke ntawm clopidogrel nrog tshuaj tiv thaiv qhov ncauj tsis pom zoo, vim tias qhov kev sib txuam no tuaj yeem ua rau ntau ntxiv los ntshav. Dua li ntawm qhov tseeb tias kev siv clopidogrel ntawm ib koob ntawm 75 mg rau ib hnub tsis pauv pauv pharmacokinetic profile ntawm S-warfarin lossis kev tiv thaiv kab mob thoob ntiaj teb (INR) hauv cov neeg mob uas tau siv tshuaj warfarin tau ntev, kev siv ib txhij ntawm clopidogrel thiab warfarin ua rau muaj kev pheej hmoo los ntshav vim los ntawm ywj pheej cuam tshuam rau hemostasis.

Tus Neeg Glycoprotein IIb Tus Ua Yeeb Yam, / IIIA Cov. Clopidogrel yuav tsum siv nrog ceev faj hauv cov neeg mob uas muaj kev pheej hmoo ntxiv los ntshav vim los ntawm kev raug mob, phais lossis lwm yam kab mob pathological uas glycoprotein IIb, / IIIA inhibitors tau ib txhij.

Acetylsalicylic acid (ASA). Acetylsalicylic acid tsis hloov pauv kev cuam tshuam ntawm clopidogrel ntawm ADP-vim platelet aggregation, tab sis clopidogrel ntxiv cov nyhuv ntawm ASA rau ntawm collagen hob platelet aggregation. Txawm li cas los xij, kev siv ib txhij ntawm 500 mg ntawm ASA 2 zaug hauv ib hnub rau ib hnub tsis ua rau muaj qhov tseem ceeb hauv lub sijhawm los ntshav, lub sijhawm ntev vim clopidogrel. Txij li thaum pharmacodynamic kev sib cuam tshuam ntawm clopidogrel thiab acetylsalicylic acid muaj peev xwm ua tau nrog kev pheej hmoo los ntshav ntau, kev siv cov tshuaj no ib zaug yuav tsum ceev faj.Dua li ntawm qhov no, muaj kev paub txog kev noj clopidogrel thiab ASA ua ke txog li ib xyoos.

Heparin. Nws tau tshaj tawm tias clopidogrel tsis xav tau koob kho ntawm heparin thiab tsis cuam tshuam rau cov nyhuv ntawm heparin ntawm kev sib tsoo. Kev siv txhij ib txhij ntawm heparin tsis hloov pauv qhov cuam tshuam ntawm clopidogrel ntawm platelet aggregation. Txij li thaum pharmacodynamic kev sib cuam tshuam ntawm clopidogrel thiab heparin muaj peev xwm ua tau nrog kev pheej hmoo los ntshav ntau, kev siv cov tshuaj no ib zaug yuav tsum ceeb toom.

Thrombolytic tus neeg sawv cev. Kev nyab xeeb ntawm kev siv tib txhij ntawm clopidogrel, fibrin-specific lossis fibrin-specific thrombolytic cov neeg sawv cev thiab heparin tau tshawb xyuas hauv cov neeg mob uas muaj myocardial infarction. Qhov ntau zaus los ntshav tseem ceeb ntawm kev kuaj ntshav tau zoo ib yam li tau pom nrog kev siv cov tshuaj thrombolytic thiab heparin nrog ASA.

Nonsteroidal anti-inflammatory tshuaj (NSAIDs). Qhov kev siv ntau tshaj plaws ntawm clopidogrel thiab naproxen tau tshaj tawm tias ua rau muaj kev mob ntsws ntau ntau los ntshav. Txawm li cas los xij, vim tias tsis muaj kev kawm txog kev sib cuam tshuam ntawm cov tshuaj nrog lwm cov NSAIDs, nws tseem tsis tau meej meej, qhov kev pheej hmoo ntawm txoj hnyuv ntshav nce ntxiv thaum siv nrog txhua NSAIDs. Yog li, kev ceev faj yog qhov tsim nyog thaum siv NSAIDs, tshwj xeeb COX-2 inhibitors, nrog clopidogrel.

Xaiv Serotonin Reuptake Inhibitors (SSRIs). Muab hais tias SSRIs cuam tshuam platelet kev ua kom lub cev thiab ua rau muaj kev pheej hmoo los ntshav, kev siv SSRIs ib txhij nrog clopidogrel yuav tsum ceev faj.

Proton twj tso kua mis (PPIs).

Qhov kev sib zog ntawm cov tshuaj metabolite hauv cov ntshav txo qis nrog kev siv tib lub sijhawm los yog 12-teev sib nrug ntawm koob tshuaj clopidogrel thiab omeprazole hauv koob tshuaj 80 mg. Qhov kev txo qis no tau nrog los ntawm kev txo qis hauv kev txo cov platelet aggregation. Esomeprazole yuav tsum nkag mus rau hauv kev sib txuam zoo ib yam nrog clopidogrel.

Cov ntaub ntawv tsis meej xwm tau qhia txog kev sib raug zoo ntawm pharmacodynamic / pharmacokinetic thiab kev pheej hmoo mob plawv. Hauv qhov no, clopidogrel nrog omeprazole lossis esomeprazole yuav tsum siv nrog ceev faj.

Ib qhov tsawg tshaj tawm tsawg dua hauv kev mloog zoo ntawm cov metabolite hauv cov ntshav tau pom nrog pantoprazole lossis lansoprazole. Clopidogrel tuaj yeem siv nrog pantoprazole.

Tsis muaj pov thawj ntxiv tias lwm cov kua qaub-txo cov tshuaj, xws li cov tshuaj tiv thaiv proton twj tso kua mis los yog antacids, cuam tshuam rau kev ua los ntawm kev tawm tsam ntawm clopidogrel.

Antacids tsis cuam tshuam rau qib ntawm kev nqus ntawm clopidogrel.

Ua ke nrog lwm cov tshuaj. Txij li thaum clopidogrel hloov mus rau hauv nws cov nquag metabolite ib feem nyob rau hauv kev cuam tshuam ntawm CYP2C19, kev siv cov tshuaj uas txo qis cov kev ua haujlwm ntawm cov enzyme no yuav ua rau txo qis ntawm cov tshuaj lom neeg ntawm cov metabolite ntawm clopidogrel hauv ntshav. Cov kab mob tseem ceeb hauv kev cuam tshuam ntawm no tsis tau elucidated. Yog li, raws li kev tiv thaiv kev tiv thaiv, kev siv tib lub sijhawm muaj zog thiab muaj zog CYP2C19 inhibitors yuav tsum zam.

Kev npaj uas muaj hwj chim lossis txwv hnyav ntawm CYP2C19 kev ua haujlwm suav nrog omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, carbamazepine thiab efavirenz.

Clinically tseem ceeb kev sib txuam chaw muag tshuaj thaum siv clopidogrel ib txhij nrog atenolol, nifedipine lossis nrog ob qho tshuaj yeeb tsis tau kuaj. Tsis tas li ntawd, pharmacodynamic kev ua haujlwm ntawm clopidogrel tseem nyob zoo yam tsis hloov thaum siv phenobarbital thiab estrogen .

Cov chaw muag tshuaj digoxin lossis theophylline tsis tau hloov nrog kev siv txoom nrog clopidogrel.

Carboxylic clopidogrel metabolites tuaj yeem tiv thaiv kev ua si ntawm cytochrome P450 2C9.Qhov no muaj peev xwm ua kom nce qib ntshav ntxiv ntawm cov tshuaj nyiam phenytoin thiab tolbutamide, thiab lwm tus uas tau metabolized siv cytochrome P450 2C9. Dua li ntawm no, cov txiaj ntsig tau los ntawm kev tshawb fawb tshawb pom tias phenytoin thiab tolbutamide tuaj yeem siv nrog kev nyab xeeb nrog clopidogrel.

Cov tshuaj uas yog substrates ntawm cytochrome CYP2C8

Clopidogrel tau tshaj tawm tias nce repaglinide nthuav dav hauv cov neeg tuaj yeem noj qab haus huv. Kev siv ib txhij ntawm clopidogrel thiab cov tshuaj uas feem ntau cuam tshuam los ntawm CYP2C8 cytochrome (e.g. repaglinide, paclitaxel) yuav tsum tau ua nrog ceev faj, muab qhov kev pheej hmoo ntawm kev nce lawv cov siab hauv ntshav ntshav.

Tsuas yog zam ntawm cov ntaub ntawv hais txog kev cuam tshuam nrog rau cov tshuaj tshwj xeeb tau muab rau saum toj no, kev tshawb fawb txog kev cuam tshuam ntawm clopidogrel nrog cov tshuaj uas feem ntau tau muab rau cov neeg mob atherothrombosis tsis tau ua. Txawm li cas los xij, cov neeg mob uas tau koom nrog kev tshawb nrhiav kev kho mob ntawm clopidogrel siv lwm yam tshuaj rau tib lub sijhawm, suav nrog diuretics, beta-blockers, ACE inhibitors, calcium antagonists, cholesterol txo qis tshuaj, mob ntshav vasodilators, tshuaj tiv thaiv kab mob (nrog rau cov tshuaj insulin), cov tshuaj antiepileptic, kev hloov tshuaj kho thiab GPIIb / IIIa antagonists, uas tsis muaj cov pov thawj ntawm cov kab mob tseem ceeb hauv kev mob loj.