Zaltrap ya mankhwala: malangizo ogwiritsira ntchito

Zina zamalonda zamankhwala: Zaltrap

Dzinalo Lopanda Padziko Lonse: Aflibercept

Fomu ya Mlingo: kulowetsedwa njira yang'anani

Chithandizo: chidziwitso

Gulu la Pharmacotherapeutic: antitumor wothandizira

Katundu

Mankhwala a Antitumor. Aflibercept ndi puloteni yosakanikirana ya fusion yopanga VEGF (endothelial vascular grow factor) yomanga magawo ena a zigawo za extracellular za VEGF 1 receptor ndi VEGF 2 receptor yolumikizidwa ku Fc domain (chidutswa cha cholephera kuzimitsa) cha immunoglobulin G1 (IgG1). Aflibercept imapangidwa pogwiritsa ntchito ukadaulo wa DNA wogwiritsa ntchito njira ya Chinese hamster ovary cell expression (CHO) K-1. Aflibercept ndi chimeric glycoprotein wolemera maselo 97 kDa, mapuloteni glycosylation amawonjezera 15% kulemera kokwanira kwamolekyulu, zomwe zimapangitsa kulemera kwathunthu kwa aflibercept ya 115 kDa. Endothelial vascular grow factor A (VEGF-A), endothelial vascular grow factor B (VEGF-B) and placental grow factor (P1GF) ali m'gulu la VEGF-banja la angiogenic zinthu zomwe zimatha kukhala zinthu zolimba ngati mitogenic, chemotactic komanso mtima. maselo endothelial. VEGF-A imagwira ntchito kudzera m'magulu awiri a receptor tyrosine kinases - VEGFR-1 ndi VEGFR-2, yomwe ili pamaselo a maselo a endothelial. P1GF ndi VEGF-B amamangirira kokha kwa VEGFR-1 receptor tyrosine kinase, yomwe, kuphatikiza pamaso pa maselo a endothelial, imapezekanso pamwamba pa leukocytes. Kuchuluka kwa izi VEGF-A zolandilira kungayambitse matenda a m'mitsempha komanso kuchuluka kwa mtima. P1GF imakhudzanso ndikukula kwa pathological neovascularization ndi chotupa kulowa mkati mwa maselo otupa. Aflibercept imakhala ngati "receptor-trap" yosungunuka yomwe imamangiriza ku VEGF-A yothandizana kwambiri kuposa VEGF-A receptors, kuwonjezera apo imamangirizanso ndi ligands VEGF-B ndi P1GF. Aflibercept imamangilira anthu VEGF-A, VEGF-B ndi P1GF ndikupanga mapangidwe olimba a inert zovuta omwe alibe ntchito yachilengedwe. Kuchita ngati "msampha" wamatumbo, maulalo kumalepheretsa kulumikizana kwa zigwirizano zam'manja kuzinthu zawo, ndipo potero zimalepheretsa kufalikira kwa ma siginolo kudzera pama receptor awa. Aflibercept imalepheretsa kutseguka kwa ma VEGF receptors komanso kuchuluka kwa maselo a endothelial, potero akuletsa mapangidwe atsopano otumiza chotupacho ndi mpweya ndi michere. Aflibercept imamangilira anthu VEGF-A (the equilibrium dissociation frequ (Cd) ndi 0,5 pmol kwa VEGF-A165 ndi 0.36 pmol kwa VEGF-A121), kwa anthu P1GF (Cd 39 pmol to P1GF-2), to VEGF-B (Cd human) 1.92 pmol) ndikupanga khola lolimba la inert lomwe lilibe zochita zenizeni zachilengedwe.

Zisonyezo zogwiritsidwa ntchito:

Metastatic colorectal cancer (MKRP) (mwa odwala okalamba) yogonjetsedwa ndi chemalipapy yokhala ndi oxaliplatin kapena kupita patsogolo pambuyo pa kugwiritsidwa ntchito kwake (Zaltrap kuphatikiza ndi regimen kuphatikizapo irinotecan, fluorouracil, calcium folinate (FOLFIRI).

Zoyipa:

Hypersensitivity to entlibercept or any of pounsels Zaltrap, magazi kwambiri, ochepa matenda oopsa, osagwirizana ndi mankhwala, mtima wosalephera wa gulu la III-IV (gulu la NYHA), kufooka kwambiri kwa chiwindi (kusowa kwa chidziwitso) kuyambitsa thupi vitreous (chifukwa cha hyperosmotic zimatha mankhwala Zaltrap), mimba, nthawi yoyamwitsa, ana ndi achinyamata Ast zaka 18 (chifukwa cha kusowa zinachitikira okwanira mu ntchito).Chenjezo: Kulephera kwa aimpso, matenda oopsa, matenda oopsa a mtima (CHD, kuperewera kwamatenda oyamba a mtima I-II malinga ndi gulu la NYHA), ukalamba, zikhalidwe zambiri ≥2 pamlingo wowunika momwe wodwalayo alili ECOG ( Gulu Lamadongosolo Ogwirizana a Eastern).

Mlingo ndi makonzedwe:

Zaltrap imayendetsedwa iv m'njira ya kulowetsedwa kwa ola limodzi, kenako ndikugwiritsa ntchito chemotherapeutic regimen FOLFIRI. Mlingo wovomerezeka wa Zaltrap wophatikizira ndi chemotherapeutic regimen FOLFIRI ndi 4 mg / kg kulemera kwa thupi. FOLFIRI chemotherapeutic regimen: tsiku loyamba la kuzungulira - munthawi yomweyo iv kulowetsedwa kudzera mu mawonekedwe a Y-irinotecan catheter pa mlingo wa 180 mg / m2 kwa 90 min ndi calcium folute (kumanzere- ndi kumanzere kwamanja) pamankhwala a 400 mg / m2 kwa maola 2 , kutsatiridwa ndi iv (bolus) makonzedwe a fluorouracil pa mlingo wa 400 mg / m2, ndikutsatira kulowetsedwa kosalekeza kwa fluorouracil pa mlingo wa 2400 mg / m2 kwa maola 46. Makina a chemotherapy amabwerezedwanso sabata iliyonse 2. Kuchiza ndi Zaltrap kuyenera kupitilizidwa mpaka matendawa atakula kapena pakakhala vuto losavulaza.

Zotsatira zoyipa:

Zowopsa zomwe zimawonedwa pafupipafupi kwambiri (HP) zama degree onse azovuta (zomwe zimachitika pafupipafupi ndi ≥20%) ndizodziwika bwino kwambiri ndi Zaltrap / FOLFIRI chemotherapeutic regimen kuposa FOLFIRI chemotherapeutic regimen (m'njira yocheperako): leukopenia, kutsekula m'mimba, neutropenia, proteinuria, kuchuluka kwa ntchito ya ACT, stomatitis, kutopa, thrombocytopenia, kuchuluka kwa ntchito za ALT, kuchuluka kwa kuthamanga kwa magazi, kuchepa thupi, kuchepa kudya, mphuno zam'mimba, kupweteka kwam'mimba, kukomoka, kuchuluka serum creatinine ndi mutu. Nthawi zambiri, ma HPs otsatira a kuopsa kwa 3-4 (omwe amakhala ndi ≥5%) amawonetsedwa, pafupifupi 2% nthawi zambiri ndi Zaltrap / FOLFIRI chemotherapeutic regimen kuposa FOLFIRI chemotherapeutic regimen (pofuna kuchepetsa kufalikira): neutropenia, kutsegula m'mimba, kuthamanga kwa magazi, leukopenia, stomatitis, kutopa, proteinuria ndi asthenia. Mwambiri, kusiya kwa mankhwalawa chifukwa cha zovuta zomwe zachitika (zama degree onse azovuta) zinaonedwa mu 26.8% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen poyerekeza ndi 12.1% ya odwala omwe amalandira FOLFIRI chemotherapy regimen. HP yodziwika kwambiri yomwe idayambitsa kukanidwa kwa mankhwalawa mu ≥1% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen anali asthenia / kutopa, matenda, kutsegula m'mimba, kuchepa kwa magazi, kuthamanga kwa magazi, stomatitis, zovuta za venous thromboembolic, neutropenia ndi proteinuria. Mlingo kusintha kwa mankhwala Zaltrap (kuchepetsa mlingo ndi / kapena zosiyidwa) kunachitika mu 16,7%. Kuwongolera kwazotsatira zamankhwala othandizira kupitirira masiku 7 kunawonedwa mu 59.7% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen poyerekeza ndi 42.6% ya odwala omwe amalandira FOLFIRI chemotherapy regimen. Imfa ya zoyambitsa zina, kupatula imfa chifukwa cha kudwala kwamatenda, yowonekera mkati mwa masiku 30 pambuyo poti magawo omaliza a chemotherapeutic regimen adalembedwa mu 2.6% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen komanso mu 1.0% ya odwala omwe amalandira FOLFIRI chemotherapy regimen. Choyambitsa kufa kwa odwala omwe amalandila mankhwala a Zaltrap / FOLFIRI chemotherapy anali matenda (kuphatikizapo neutropenic sepsis) mwa 4 odwala, kuchepa kwa madzi mu 2 odwala, hypovolemia mu 1 wodwala, metabolic encephalopathy mu 1 wodwala, kupuma kwamatenda matenda; kufunafuna chibayo, ndi pulmonary thromboembolism) mwa odwala atatu, zotupa zam'mimba (magazi am'mimba kuchokera m'matumbo am'mimba, kutupa kwam'mimba thirakiti, kulowetsa matumbo kwathunthu) mwa odwala atatu, kufa kwa odwala osadziwika Fikirani odwala 2.Zowopsa za HP ndi labotale zomwe zimawonedwa mwa odwala omwe amathandizidwa ndi Zaltrap / FOLFIRI chemotherapy regimen (malinga ndi MedDRA) zimawonetsedwa pansipa. Zambiri za HP zimatanthauzidwa ngati zovuta zilizonse zachipatala kapena zodabwitsazo mu magawo a labotale, ma frequency omwe anali ≥2% apamwamba (a HP of degrees all the severity) mu gulu la aflibercept poyerekeza ndi gulu la placebo mu kafukufuku wopangidwa mwa odwala omwe ali ndi ICP. Mphamvu ya HP idayikidwa malinga ndi NCI CTC (National Cancer Institute General Toxicity Rating Scale) mtundu wa 3.0. Kuwona kuchuluka kwa HP (malinga ndi gulu la WHO): pafupipafupi (≥10%), nthawi zambiri (≥1% - madigiri 3 kuzunza kwambiri), nthawi zambiri asthenic mamiriro (≥3 madigiri akuuma), mwapang'onopang'ono - kuchiritsa kwamabala , kulephera kwa anastomoses) (madigiri onse azovuta ndi ≥3 madigiri akuya).

Zolemba zowerengera ndi zothandizira: pafupipafupi - ntchito yowonjezereka ya ACT, ALT (madigiri onse azovuta), kuchepa kwa thupi (madigiri onse azovuta), nthawi zambiri - ntchito yowonjezereka ya ACT, ALT ≥3 madigiri akuya, kuchepa kwa thupi madigiri ≥3.

Mogwirizana ndi mankhwala ena:

Kafukufuku wokhawokha wochita mogwirizana ndi mankhwala ndi Zaltrap sanachitike. Kafukufuku wofanizira, kutsata kwaulere komanso kumangika kwa aflibercept kuphatikiza ndi mankhwala ena kunali kofanana ndi kuzama kwa aflibercept ndi monotherapy, zomwe zikuwonetsa kuti kuphatikiza uku (oxaliplatin, cisplatin, fluorouracil, irinotecan, docetaxel, pemetrexed, gemcitabine ndi erlotinib) sizikhudza pharmacokine aflibercepta. Aflibercept, sizinakhudze pharmacokinetics ya irinotecan, fluorouracil, oxaliplatin, cisplatin, docetaxel, pemetrexed, gemcitabine, ndi erlotinib.

Tsiku lotha ntchito: Zaka zitatu

Mankhwala Okhala Pamalo a Pharmacy: mwa kulemba

Contraindication

- Hypersensitivity kuti aflibercept kapena aliyense wokonda mankhwala,

- matenda oopsa, osavomerezeka pakuwongolera madokotala,

- kulephera kwamtima kwa mtima kwa III-IV kalasi (gulu la NYHA),

- Kulephera kwamphamvu kwa chiwindi (kusowa kwa chidziwitso pakugwiritsa ntchito),

- ntchito kwa ophthalmic kapena makonzedwe a thupi lamphamvu (chifukwa cha Hyperosmotic katundu wa mankhwala),

- nthawi yoyamwitsa,

- ana ndi achinyamata osakwana zaka 18 (chifukwa cha kusowa kwa chidziwitso chokwanira).

kulephera kwambiri kwa aimpso,

- matenda ofunikira a mtima dongosolo (matenda a mtima, matenda a mtima osalephera I-II malinga ndi gulu la NYHA),

- mawonekedwe onse> Ma 2 pang'onopang'ono kuti athe kuwunika wodwala ECOG wodwala (Eastern United Gulu la Oncologists).

Momwe mungagwiritsire ntchito: Mlingo ndi njira ya chithandizo

Mitsempha monga kulowetsedwa kwa ola limodzi, kenako ndikugwiritsira ntchito chemotherapeutic regimen FOLFIRI.

Mlingo woyenera wophatikizidwa ndi FOLFIRI chemotherapeutic regimen ndi kulemera kwa thupi kwa 4 mg / kg.

Chemotherapy scheme FOLFIRI:

patsiku loyamba la kuzungulira - kulowetsedwa munthawi yomweyo kudzera m'mitsempha ya Yinotecan pa mlingo wa 180 mg / m2 kwa mphindi 90 ndi calcium folule (kumanzere kumanja kwa mpikisano) pamankhwala a 400 mg / m2 kwa maola awiri, ndikutsatiridwa ndi mtsempha wamitsempha. ) kuyambitsa fluorouracil pa mlingo wa 400 mg / m2, kenako kulowetsedwa mosalekeza kulowetsedwa kwa fluorouracil pa mlingo wa 2400 mg / m2 kwa maola 46.

Zozungulira za chemotherapy zimabwerezedwa masabata awiri aliwonse.

Chithandizo chikuyenera kupitilizidwa mpaka matenda atakula kapena pakakhala vuto lovuta.

Malangizo pakuwongolera dosing regimen / kuchedwa kwa chithandizo

Chithandizo ziyenera kutha:

- ndi kukula kwa magazi kwambiri,

- ndi chitukuko cha kukonzanso kwa makhoma am'mimba,

- ndikupanga fistula,

- ndi chitukuko cha matenda oopsa kapena matenda oopsa a m'mimba,

- ndi chitukuko cha ochepa thromboembolic zovuta,

- ndikupanga nephrotic syndrome kapena thrombotic microangiopathy,

- ndi kukula kwambiri hypersensitivity zimachitika (kuphatikizapo bronchospasm, kufupika kwa mpweya, angioedema, anaphylaxis),

- kuphwanya machiritso a bala omwe amafunikira chithandizo chamankhwala,

- ndikupanga njira yosinthira posterior encephalopathy syndrome (POPs), yotchedwanso posterior leukoencephalopathy (POPs).

Osachepera milungu 4 ntchito isanachitike, chithandizo ndi Zaltrap ziyenera kuyimitsidwa kwakanthawi.

Kuchedwa chemotherapy Zaltrap / FOLFIRI

Neutropenia kapena thrombocytopenia: Kugwiritsira ntchito kwa mankhwala a Zaltrap / FOLFIRI chemotherapeutic regulen kuyenera kuchepetsedwa mpaka kuchuluka kwa neutrophils m'mitsempha yamapazi kumawonjezeka mpaka>> 1500 / μl ndi / kapena kuchuluka kwa mapuloteni m'magazi oyandikira.

Zochitika modekha kapena zolimbitsa thupi (kuphatikizapo kutupira pakhungu, zotupa, uritisaria, ndi pruritus): Chithandizo chake chiyenera kuyimitsidwa kwakanthawi mpaka chithe. Ngati ndi kotheka, kuyimitsa hypersensitivity reaction, ndikotheka kugwiritsa ntchito GCS ndi / kapena antihistamines.

Pazinthu zotsatira, mutha kuganizira za kukonzekera kwa GCS ndi / kapena antihistamines.

Mitundu ikuluikulu ya Hypersensitivity reaction (kuphatikizapo bronchospasm, dyspnea, angioedema, ndi anaphylaxis): Mankhwala a chemotherapy regimen Zaltrap / FOLFIRI amayenera kusiyidwa ndipo chithandizo chakuletsa kuyimitsa hypersensitivity reaction iyenera kutha.

Kuchira pambuyo pa chithandizo ndi Zaltrap ndi kusintha kwa mlingo

Kuchuluka kwa kuthamanga kwa magazi: Muyenera kuyimitsa kanthawi kogwiritsa ntchito mankhwalawa kufikira mutayang'anira kuwonjezeka kwa kuthamanga kwa magazi.

Ndi kukonzanso mobwerezabwereza kowonjezereka kwa kuthamanga kwa magazi, kugwiritsa ntchito mankhwalawa kuyenera kuyimitsidwa mpaka chiwongolero chowonjezeka cha kuthamanga kwa magazi chikwaniritsidwe komanso m'zotsatira zake zotsika zimachepetsa mlingo wake mpaka 2 mg / kg thupi.

Proteinuria: Ndikofunikira kuyimitsa kugwiritsa ntchito mankhwala a proteinuria> 2 g / tsiku, kuyambiranso kwa mankhwalawa ndikotheka pambuyo pochepetsa proteinuria mpaka 2 g / tsiku; kugwiritsa ntchito Zaltrap kuyenera kuyimitsidwa mpaka proteinuria itachepa 20%, osachepera 2% pafupipafupi pogwiritsa ntchito mankhwala a chemotherapy regimen Zaltrap / FOLFIRI kuposa FOLFIRI chemotherapeutic regimen (pakuchepetsa kwa zochitika): leukopenia, kutsegula m'mimba, neutropenia, proteinuria, kuchuluka kwa ntchito ya ACT, stomatitis, kutopa, thrombocytopenia Alt, kuthamanga magazi, kuwonda, utachepa kudya, epistaxis, kupweteka m'mimba, dysphonia, kuchuluka creatinine seramu ndende ndi mutu.

Ma HPs otsatira a kuopsa kwa 3-4 anali kuwonedwa pafupipafupi (ndi pafupipafupi> 5%), osachepera 2% nthawi zambiri mukamagwiritsa ntchito njira ya Zaltrap / FOLFIRI chemotherapeutic regimen pogwiritsa ntchito FOLFIRI chemotherapeutic regimen (kuti muchepetse kuchuluka kwake): neutropenia, kutsegula m'mimba, kuthamanga kwa magazi, leukopenia, stomatitis, kutopa, proteinuria ndi asthenia.

Mwambiri, kusiya kwa mankhwalawa chifukwa cha zovuta zomwe zachitika (zama degree onse azovuta) zinaonedwa mu 26.8% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen poyerekeza ndi 12.1% ya odwala omwe amalandira FOLFIRI chemotherapy regimen.

HP yodziwika kwambiri yomwe idayambitsa kusiyidwa kwa chithandizo cha mankhwala> 1% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen anali asthenia / kutopa, matenda, kutsegula m'mimba, kuchepa kwa magazi, kuthamanga kwa magazi, stomatitis, venous thromboembolic zovuta, neutropenia ndi proteinuria.

Kusintha kwa Mlingo (kuchepetsa kumwa ndi / kapena zosiyidwa) kunachitika mu 16,7%. Kuwongolera kwazotsatira zamankhwala othandizira kupitirira masiku 7 kunawonedwa mu 59.7% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen poyerekeza ndi 42.6% ya odwala omwe amalandira FOLFIRI chemotherapy regimen.

Imfa ya zoyambitsa zina, kupatula imfa chifukwa cha kudwala kwamatenda, yowonekera mkati mwa masiku 30 pambuyo poti magawo omaliza a chemotherapeutic regimen adalembedwa mu 2.6% ya odwala omwe amalandila Zaltrap / FOLFIRI chemotherapy regimen komanso mu 1.0% ya odwala omwe amalandira FOLFIRI chemotherapy regimen. Zomwe zimapangitsa odwala omwe amalandila mankhwala a Zaltrap / FOLFIRI chemotherapy anali matenda (kuphatikizapo neutropenic sepsis) mwa 4 odwala, kuchepa kwa madzi mu 2 odwala, hypovolemia mu 1 wodwala, metabolic encephalopathy mu 1 wodwala, kupuma thirakiti matenda (kupweteka kwambiri kupuma, chibayo) ndi pulmonary embolism) mwa odwala atatu, zotupa zam'mimba (magazi am'mimba, zilonda zam'mimba, kutupa kwamatumbo kwathunthu) mwa odwala atatu, zotsatira zakupha kuchokera kusadziwika zifukwa zowonekera mwa odwala 2.

Zowopsa za HP ndi labotale zomwe zimawonedwa mwa odwala omwe amathandizidwa ndi Zaltrap / FOLFIRI chemotherapy regimen (malinga ndi MedDRA) zimawonetsedwa pansipa. Zambiri za HP zimatanthauzidwa ngati zovuta zilizonse zachipatala kapena zoopsa m'magawo a labotale, zomwe zimachitika pafupipafupi> 2% (kwa HP ya magawo azovuta zonse) m'gululi lodziyerekeza ndi gulu la placebo mu kafukufuku wopangidwa mwa odwala omwe ali ndi ICP. Mphamvu ya HP idayikidwa malinga ndi NCI CTC (National Cancer Institute General Toxicity Rating Scale) mtundu wa 3.0.

Kudziwitsa pafupipafupi kwa HP (malinga ndi gulu la WHO): pafupipafupi (> 10%), nthawi zambiri (> 1% - 0,1% - 0,01% - magawo atatu azovuta).

Kuchokera pamagazi ndi mitsempha yam'mimba: kawirikawiri - leukopenia (madigiri onse azakhungu ndi> ma degree atatu a kuvuta), neutropenia (madigiri onse azovuta ndi> madigiri 3 mwamphamvu), thrombocytopenia (madigiri onse osautsa), nthawi zambiri - febrile neutropenia ya madigiri onse azakhungu ndi> 3 madigiri owopsa, thrombocytopenia> madigiri 3 mwamphamvu.

Pa chitetezo cha mthupi: Nthawi zambiri - mphamvu ya Hypersensitivity (madigiri onse azikhala mwamphamvu), modabwitsa - hypersensitivity reaction> madigirii atatu azovuta.

Kuchokera kumbali ya kagayidwe kachakudya ndi zakudya: pafupipafupi - kuchepa kwa chidwi (madigiri onse azovuta), nthawi zambiri - kusowa kwamphamvu (madigiri onse azovuta ndi> madigiri 3 mwamphamvu), kusowa kwa chilimbikitso> madigiri atatu mwamphamvu.

Kuchokera kumbali yamanjenje: pafupipafupi - kupweteka mutu (kwa madigiri onse azovuta), nthawi zambiri - kupweteka kwamutu> madigiri atatu mwamphamvu, modabwitsa - posinthira posterior encephalopathy syndrome (SARS).

Kuchokera pamtima dongosolo: pafupipafupi - kuthamanga kwa magazi (madigiri onse azovuta) (mu 54% ya odwala omwe amawonjezera kuthamanga kwa magazi> madigiri atatu mwamphamvu, kuwonjezeka kwa kuthamanga kwa magazi komwe kumachitika munthawi ya njira ziwiri zoyambirira zamankhwala), magazi / hemorrhage (madigiri onse kuvuta), mtundu wofala kwambiri wamatenda akuchepa m'mphuno (ma degree 1-2 a kuvuta), nthawi zambiri umagwirizana ndi mavuto ena (ATEO) (monga zovuta pachimake, kuphatikiza misala, angina pectoris, intracardiac thrombus, myocardial infarction, ochepa thromboembolism ndi ischemic colitis) (madigiri onse azovuta zamkati), venous thromboembolic complication (VTEO) (deep vein thrombosis and pulmonary embolism) ya magawo onse azakhungu, magazi> zaka zitatu, mwamphamvu. kuphatikiza magazi am'mimba, hematuria, magazi pambuyo pa njira zachipatala, kusadziwika pafupipafupi - mwa odwala omwe alandila Zaltrap, kukulira kwa hemorrhage kwamkati kwambiri ndi mapapu ny / hemoptysis, kuphatikizapo zotsatira zakupha.

Kuchokera pakapumidwe: Nthawi zambiri - kupuma movutikira (kwa madigiri onse azovuta zamkati), nosebleeds (wa madigiri onse azovuta), dysphonia (madigiri onse azovuta), nthawi zambiri - kupweteka kwa oropharynx (madigiri onse osautsa), rhinorrhea (ma rhinorrhea awiri okha kuzika), kuperewera - kupuma movutikira> ma degree atatu, kuuma, ma degree 3> kuzungulira, kupsinjika> madigirii atatu a kupweteka, kupweteka kwa oropharynx> madigirii atatu.

Kuchokera pamimba yodyetsera: pafupipafupi - kutsekula m'mimba (madigiri onse azakhungu)> digatitis (madigiri onse azovuta ndi> madigiri atatu akuya), kupweteka kwam'mimba (madigiri onse ozunza), kupweteka pamimba pamimba (madigiri onse azovuta) , kawirikawiri - kupweteka kwam'mimba> madigiri atatu a kupsinjika, kupweteka kwam'mimba> ma degree atatu a kupsinjika, ma hemorrhoids (madigiri onse azovuta), magazi ochokera ku rectum (madigiri onse azovuta), kupweteka kwa rectum (madigiri onse azovuta), kupweteka kwameno ( madigiri onse azovuta), aphthous stomatitis (madigiri onse azovuta kudya), mapangidwe a fistulas (kumatako, matumbo amkodzo, kunja kwamkati wamatumbo ang'ono-khungu, colonic-vaginal, matumbo) (madigiri onse azakhungu), modabwitsa - mapangidwe am'mimba a fistulas> madigirii atatu a kuopsa, kutsuka kwa makoma am'mimba mwa madigiri onse 3 madigiri akuthwa, kuphatikiza kununkhira kwa makoma am'mimba, kutuluka magazi kuchokera ku rectum> madigiri atatu a kupsinjika, aphthous stomatitis> madigiri atatu a kupweteka, kupweteka kwa rectum> madigiri atatu.

Kuchokera pakhungu ndi minyewa yolumikizana: pafupipafupi - kanjedza kamtundu wa erythrodysesthesia syndrome (madigiri onse azovuta), nthawi zambiri - khungu hyperpigmentation (madigiri onse azovuta), masamba a erythrodysesthesia syndrome> ma degree atatu.

Kuchokera kwamikodzo dongosolo: pafupipafupi - proteinuria (malinga ndi kuchuluka kophatikizika kwa matenda ndi ma labotale) (madigiri onse azovuta), kuchuluka kwa serum creatinine ndende (madigiri onse azovuta), nthawi zambiri - proteinuria> madigiri atatu mwamphamvu, infrequent - nephrotic syndrome. Wodwala m'modzi wokhala ndi proteinuria komanso kuchuluka kwa kuthamanga kwa magazi mwa odwala 611 omwe adalandira chithandizo cha mankhwala a Zaltrap / FOLFIRI chemotherapy regimen adapezeka kuti ali ndi thrombotic microangiopathy.

Zotsatira zambiri: pafupipafupi - mkhalidwe wa asthenic (madigiri onse azovuta), kumva kutopa (madigiri onse ozungulira ndi kuzungulira kwamphamvu), pafupipafupi - mikhalidwe yodutsa (> madigiri atatu mwamphamvu), mwapang'onopang'ono - kuchiritsa kwa mabala (kupindika kwa m'mbali mwa bala, kulephera kwa anastomoses ) (madigiri onse azovuta kwambiri>> madigiri 3 mwamphamvu).

Zowerengera zamankhwala othandizira ndi othandizira: pafupipafupi - ntchito yowonjezereka ya ACT, ALT (madigiri onse azovuta), kuchepa kwa thupi (madigiri onse azovuta), kawirikawiri - ntchito yowonjezera ya ACT, ALT> madigiri 3 kuzunza kwambiri.

Pafupipafupi pamavuto obwera m'magulu apadera odwala

Odwala okalamba (> zaka 65), kuchuluka kwa matenda otsegula m'mimba, chizungulire, asthenia, kuchepa thupi komanso kuchepa thupi kunaposa 5% kuposa odwala omwe ali ndi zaka zochepa. Odwala okalamba ayenera kuyang'aniridwa bwino ndi matenda otsegula m'mimba komanso / kapena kuchepa kwamadzi.

Odwala omwe ali ndi vuto lofooka laimpso panthawi yomwe mankhwalawa adayamba, mawonekedwe a HP anali ofanana ndi omwe odwala omwe alibe kuwonongeka kwa impso panthawi yomwe adayamba. Odwala omwe ali ndi vuto lowonongeka komanso aimpso, kupezeka kwa sanali aimpso HP nthawi zambiri kuyerekeza ndi zomwe zimachitika mwa odwala popanda kulephera kwaimpso, kupatula kuwonjezeka kwa pafupipafupi kufooka kwa thupi (kwa madigiri onse azovuta) ndi> 10%.

Monga mankhwala ena onse okhala ndi mapuloteni, aflibercept ingakhale ndi chiopsezo cha immunogenicity. Mwambiri, malinga ndi zotsatira za mayeso onse a oncological, palibe wodwala aliyense yemwe adawonetsa chitetezo champhamvu kwambiri.

Palibe zambiri pa chitetezo chotenga Zaltrap mu Mlingo wopitilira 7 mg / kg kamodzi pa masabata awiri kapena 9 mg / kg kamodzi sabata iliyonse. HP yodziwika kwambiri yodziwika ndi mitundu iyi ya dosing inali yofanana ndi HP yomwe imagwiritsidwa ntchito pogwiritsa ntchito mankhwalawa.

Palibe mankhwala enieni a mankhwalawo.Ngati mankhwala osokoneza bongo, odwala amafunikira chithandizo chothandizira, makamaka kuwunika ndi kuchiza matenda oopsa oopsa komanso proteinuria. Wodwala ayenera kuyang'aniridwa bwino kuti azindikire ndi kuwunika aliyense HP.

Malangizo apadera

Musanayambe chithandizo komanso musanayambe chithandizo chatsopano chilichonse, tikulimbikitsidwa kuyezetsa magazi ndi tanthauzo la formula ya leukocyte.

Ndi chitukuko choyamba cha neutropenia> madigiri 3 mwamphamvu, kugwiritsa ntchito kwa G-CSF kuyenera kuganiziridwanso, kuwonjezera apo, mwa odwala omwe ali ndi chiopsezo chowonjezeka cha zovuta za neutropenic, kuyambitsa kwa G-CSF popewa neutropenia ndikulimbikitsidwa.

Odwala amayenera kuwunikidwa nthawi zonse kuti awone ngati ali ndi chizindikiro cha m'mimba komanso magazi ena owopsa. Aflibercept sayenera kuperekedwa kwa odwala omwe akutuluka magazi kwambiri.

Odwala ayenera kuyang'aniridwa kuti azindikire zizindikiro ndi mawonekedwe a mafuta a makoma am'mimba. Pankhani yakukwaniritsa makoma am'mimba, chithandizo chamankhwala chiyenera kusiyidwa.

Ndi chitukuko cha fistulas, mankhwalawa ndi aflibercept ayenera kusiyidwa.

Mankhwalawa ndi aflibercept, tikulimbikitsidwa kuthana ndi magazi masabata awiri aliwonse, kuphatikizapo kuwunika kuthamanga kwa magazi musanayambe kupereka mankhwala, kapena pafupipafupi malinga ndi zomwe zikuwoneka m'chipatala pochiza ndi aflibercept. Ngati magazi akuwonjezeka kwambiri pochiza ndi aflibercept, mankhwala oyenera a antihypertgency ayenera kugwiritsidwa ntchito ndipo magazi amayang'aniridwa pafupipafupi. Ndi kuchuluka kwambiri kwa magazi, mankhwalawa ndi aflibercept amayenera kuyimitsidwa mpaka magazi atachepa kufikira zomwe mukufuna, ndipo muzotsatira zotsatirazi, mlingo wa aflibercept uyenera kuchepetsedwa mpaka 2 mg / kg. Pankhani ya chitukuko cha matenda oopsa kapena matenda oopsa ochititsa chidwi pakhungu, kuyamwa kwa mankhwala omwe aflibercept kuyenera kusiyidwa.

Chenjezo liyenera kuchitidwa popereka Zaltrap kwa odwala omwe amadziwika ndi matenda amtima, monga matenda a mtima ndi mtima. Palibe mayesero azachipatala omwe amayesedwa pakupereka mankhwala kwa odwala omwe mtima wawo ukulephera kugwira ntchito kalasi III ndi IV malinga ndi gulu la NYHA.

Wodwala akayamba ATEO, chithandizo chokhala ndi aflibercept iyenera kusiyidwa.

Pamaso pa dongosolo lililonse la aflibercept, proteinuria iyenera kutsimikizika pogwiritsa ntchito mzere woyezera kapena pofufuza kuchuluka kwa mapuloteni / creatinine mu mkodzo kuti muwone kukula kapena kuchuluka kwa proteinuria. Odwala omwe ali ndi kuchuluka kwa mapuloteni / creatinine mu mkodzo> 1 ayenera kudziwa kuchuluka kwa mapuloteni mumkodzo wa tsiku ndi tsiku.

Ndi chitukuko cha nephrotic syndrome kapena thrombotic microangiopathy, mankhwalawa ndi aflibercept ayenera kusiyidwa.

Pakachitika vuto lalikulu la hypersensitivity (kuphatikizapo bronchospasm, dyspnea, angioedema ndi anaphylaxis), mankhwalawa ayenera kusiyidwa ndipo chithandizo choyenera chofuna kuletsa izi ziyenera kuyamba.

Pankhani ya kufinya kwa hypersensitivity chifukwa cha kufooka kwa mafupa (kuphatikizapo khungu hyperemia, zidzolo, urticaria, pruritus), mankhwalawa amayenera kuyimitsidwa kwakanthawi mpaka pomwe malingaliro atsimikiza. Ngati ndikofunikira kuchipatala, corticosteroids ndi / kapena antihistamines angagwiritsidwe ntchito kuletsa izi. Pazinthu zotsatira, mutha kuganizira za kukonzekera kwa GCS ndi / kapena antihistamines. Mukayambiranso chithandizo cha odwala omwe kale anali ndi vuto la hypersensitivity, muyenera kusamala, chifukwa mwa odwala ena, kukonzanso kwa hypersensitivity reaction kunawonedwa, ngakhale anali prophylaxis, kuphatikizapo kugwiritsa ntchito corticosteroids.

Kugwiritsa ntchito aflibercept kuyenera kuyimitsidwa osachepera milungu 4 pambuyo pa kuchitapo kanthu kwakukulu mpaka opaleshoniyo itachira kwathunthu. Pochita maopaleshoni ang'onoang'ono, monga kukhazikitsa chapakati venous catheter, biopsy, kupopera mano, chithandizo ndi aflibercept chitha kuyamba / kuyambiranso pambuyo poti bala la opaleshoni litachira kwathunthu.Odwala omwe ali ndi vuto la mabala akuchiritsa omwe akufuna kulowererapo kuchipatala, kugwiritsa ntchito aflibercept kuyenera kusiyidwa.

Ma POP amatha kuwonetsedwa ndi kusintha kwa malingaliro am'maganizo, khunyu, nseru, kusanza, kupweteka mutu komanso kusokonezeka kwa maonekedwe. Kuzindikira kwa LUTS kumatsimikiziridwa ndi kujambulidwa kwa MRI yaubongo. Odwala omwe ali ndi POP, kugwiritsa ntchito aflibercept kuyenera kusiyidwa.

Odwala okalamba (> azaka 65) ali ndi chiopsezo chowonjezereka cha matenda otsegula m'mimba, chizungulire, asthenia, kuchepa thupi komanso kuchepa thupi. Pofuna kuchepetsa ngozi, odwalawa amafunika kuyang'aniridwa mosamala kuti adziwe zoyambira ndi chithandizo cha zizindikiro ndi matenda am'mimba.

Odwala omwe ali ndi mndandanda wazidziwitso> ma 2 ma point (pa point-point 0-4 point test EPLG of the Eastern Joint Oncology Group) kapena omwe ali ndi matenda oyipa atha kukhala pachiwopsezo chachikulu chotsatira zovuta zamankhwala ndipo amafunika kuyang'aniridwa mosamala ndi madokotala kuti adziwe zoyipa zam'tsogolo.

Zaltrap ndi yankho la hyperosmotic, kapangidwe kake kosagwirizana ndi kuyambitsa mu intraocular space. Mankhwala sangathe kulowa mu thupi la vitreous.

Palibe maphunziro omwe adachitidwa pazotsatira za Zaltrap pazoyendetsa magalimoto kapena zochitika zina zowopsa. Ngati odwala ali ndi zizindikilo zomwe zimakhudza kuwona kwawo ndi kuthekera kwambiri, komanso kuchepetsa liwulo la psychomotor, odwala ayenera kulangizidwa kuti apewe kuyendetsa magalimoto ndi zochitika zina zomwe zingakhale zowopsa.

Mimba komanso kuyamwa

Palibe zambiri pakugwiritsa ntchito kwa amayi apakati. M'maphunziro oyesera, zotsatira za embryotoxic and teratogenic of aflibercept in wanyama zidawululidwa. Chifukwa angiogenesis ndiyofunikira kwambiri pakukula kwa mluza; kuletsa kwa angiogeneis ndi makonzedwe a Zaltrap kungayambitse mavuto osagwirizana ndi kukula kwa mimba. Kugwiritsa ntchito mankhwala pa nthawi ya pakati kumatsutsana.

Amayi a msinkhu wobereka ayenera kulangizidwa kuti apewe kutenga pakati pa mankhwala a Zaltrap. Ayenera kudziwitsidwa za kuthekera kwa zovuta pamankhwala a mwana wosabadwayo.

Amayi azaka zoyambira kubereka komanso abambo achonde ayenera kugwiritsa ntchito njira zabwino za kulera panthawi ya chithandizo komanso kwa miyezi isanu ndi umodzi itatha kumwa kwa mankhwalawo.

Pali mwayi wokhala ndi chonde chovuta kwa abambo ndi amayi munthawi yamankhwala omwe amathandizidwa ndi aflibercept (kutengera zomwe zimapezeka pofufuza zomwe zimachitika pa anyani, amuna ndi akazi omwe zomwe zimabweretsa vuto lakubala, kusinthika kwathunthu pambuyo pa masabata 8-18).

Panalibe maphunziro azachipatala omwe amayesa kuwunika kwa Zaltrap pakupanga mkaka wa m'mawere, kudzipatula kwa mkaka wam'mawere, komanso momwe mankhwalawa amathandizira akhanda.

Sizikudziwika ngati akazi ndi mkaka wa m'mawere amatha. Komabe, chifukwa chakuti sizingatheke kupatula kuthekera kolowerera mkaka wa m'mawere, komanso chifukwa chitha kukulitsa zovuta zoyipa zomwe zakumana ndi zomwe zimayambitsa makanda, ndikofunikira kukana kuyamwitsa kapena kusagwiritsa ntchito Zaltrap ( kutengera kufunikira kwa kugwiritsa ntchito mankhwalawa kwa mayi).

Kuchita

Kafukufuku wokhawokha wochita mogwirizana ndi mankhwala ndi Zaltrap sanachitike.

Mu kafukufuku woyerekeza, kutsata kwaulere ndi womangidwa mosakanikirana ndimankhwala ena kunali kofanana ndi kuzama kwa aflibercept ndi monotherapy, zomwe zikuwonetsa kuti kuphatikiza kumeneku (oxaliplatin, cisplatin, fluorouracil, irinotecan, docetaxel, pemetrexed, gemcitabine, ndi erlotinib) sizikhudza pharmacokinetics of aflibercept.

Gulu la Nosological (ICD-10)

Mankhwala

Aflibercept ndi puloteni yosakanikirana yophatikizika kwa VEGF (mtima endothelial kukula chinthuendothelial mtima kukula kwa zinthu) mbali za madera akunja a receptor VEGF-1 ndi VEGF- 2 yolumikizidwa ku tsamba la Fc (chidutswa chokhoza kuyang'ana kulira) IgG₁ munthu.

Aflibercept imapangidwa pogwiritsa ntchito ukadaulo wa DNA wogwiritsa ntchito njira ya Chinese hamster ovary cell expression (CHO) K-1.

Aflibercept ndi chimeric glycoprotein wolemera maselo 97 kDa, mapuloteni glycosylation amawonjezera 15% kulemera kokwanira kwamolekyulu, zomwe zimapangitsa kulemera kwathunthu kwa aflibercept ya 115 kDa.

Endothelial mtima kukula factor A (VEGF-A)endothelial mtima kukula factor B (VEGF-B) ndi kukula kwachulukidwe (PLGF) gwirizana ndi VEGF- banja la angiogenic zinthu zomwe zimatha kukhala wamphamvu mitogenic, chemotactic komanso mtima kupatsirana kwa zinthu za maselo a endothelial. Machitidwe VEGF-A ikuchitika kudzera awiri receptor tyrosine kinases - VEGFR-1 ndi VEGFR- yomwe ili pamtunda wa maselo a endothelial. Plgf ndi VEGF-B mangirirani kokha ku receptor tyrosine kinase VEGFR-1, yomwe, kuphatikiza pa kukhala pamtunda wa maselo a endothelial, imapezekanso pamwamba pa leukocytes. Kuchulukitsa kwakukulu kwa zolandilira izi VEGF-A kumatha kubweretsa matenda a m'mitsempha komanso kukoka kwa mtima. Plgf zokhudzana ndi kukula kwa pathological neovascularization ndi chotupa kulowetsedwa ndi maselo otupa.

Aflibercept imagwira ntchito ngati cholumikizira msampha cholandirira chomwe chimangirira VEGF-A ndi oyanjana kwambiri kuposa olandira zachilengedwe VEGF-AKupatula izi, amamanganso ndi ma ligands okhudzana VEGF-B ndi Plgf. Aflibercept imagwirizanitsidwa ndi anthu VEGF-A, VEGF-B ndi Plgf ndikupanga mapangidwe olimba a inert zovuta omwe alibe ntchito yachilengedwe. Kuchita ngati msampha wa ma ligands, aflibercept imalepheretsa kumangiriza kwa zigwirizano za amkati kuzinthu zawo zofananira ndipo potero zimaletsa kufalikira kwa zizindikiritso kudzera pama receptor awa.

Aflibercept midadula ya receptor activation VEGF Kuchulukana kwa maselo a endothelial, potero kuletsa mapangidwe atsopano otumiza chotupacho ndi mpweya ndi michere.

Aflibercept imagwirizanitsidwa ndi VEGF-A umunthu (equilibrium dissociation pafupipafupi (Cd) - 0,5 pmole wa VEGF-A165 ndi 0.36 pmol kwa VEGF-A121), s Plgf munthu (cd 39 pmol kwa Plgf-2), s VEGF-B waumunthu (Cd 1.92 pmol) ndikupanga kapangidwe ka khola la inert lomwe lilibe zinthu zachilengedwe zomwe lingatsimikizike.

Kugwiritsa ntchito maulange mu mbewa zokhala ndi xenograft kapena zotupa zam'madzi zimalepheretsa kukula kwamitundu yosiyanasiyana ya adenocarcinomas.

Odwala omwe ali ndi khansa ya metastatic colorectal (MKRP) omwe amathandizidwapo kale ndi mankhwala a oxaliplatin omwe ali ndi chemotherapy (omwe anali ndi bevacizumab kapena popanda chithandizo cham'mbuyomu), mankhwala a chemotherapy Zaltrap ® /FOLFIRI (fluorouracil, irinotecan, calcium calcium) adawonetsa kuchuluka kwamasiku amoyo poyerekeza ndi dongosolo la chemotherapeutic FOLFIRI.

Pharmacokinetics

Mafuta Mu maphunziro a preclinical omwe amapangidwa pa zitsanzo za chotupa, mapangidwe olimbitsa thupi a aflibercept adagwirizanitsidwa ndi Mlingo ofunikira kuti apange kuzungulira kwa aflibercept yoyendayenda mu kayendedwe kazinthu, kupyola kuzungulira kwa aflibercept kuzungulira kwa magazi VEGF. Zochitika zomwe zimazungulira munjira yoyendera yokhudzana ndi VEGF aflibercepta ndi kuwonjezeka kwa mlingo wake ukuwonjezeka mpaka ambiri VEGF osalumikizidwa.Kuchulukanso kwa mlingo wa aflibercept kumabweretsa chiwopsezo chodalira mlingo wa kuchuluka kwa maulamuliro oyendayenda kuzungulira kwa dongosolo komanso kungokulitsa kochepa mu ndende komwe kumayenderana VEGF aflibercepta.

Odwala, Zaltrap ® imayendetsedwa ndi mlingo wa 4 mg / kg iv pakatha milungu iwiri iliyonse, pomwe pali zochulukitsa zochulukitsa zomwe zimafalitsidwa VEGF.

Pa mlingo wovomerezeka wa 4 mg / kg kamodzi pa masabata awiri aliwonse, kuchuluka kwa aflibercept kwaulere kuli pafupi ndi mfundo za C_ss zimatheka panthawi yachiwiri ya chithandizo chamankhwala popanda kuphatikiza (kudzikwaniritsa kokwanira 1.2 muyezo wofanana, poyerekeza ndi kuchuluka kwa aflibercept jekeseni woyamba).

Kugawa. V_ss aflibercepta yaulere ndi malita 8.

Kupenda. Popeza aflibercept ndi puloteni, kafukufuku wa kagayidwe kake sanachitike. Aflibercept akuyembekezeka kugwera m'magulu ang'onoang'ono komanso ma amino acid amodzi.

Kuthetsa. The free aflibercept kuzungulira kwa kayendedwe kazinthu zimagwirizana kwambiri ndi VEGF-kamodzi ndimapangidwe osakhazikika osakhazikika. Zikuyembekezeka kuti, monga mapuloteni ena akuluakulu omwe amagwirizana nawo VEGF ndi ufulu waulere udzathetsedwa pang'onopang'ono kuchokera kuzinthu zoyenda kudzera munjira zina zachilengedwe, monga proteinolytic catabolism.

Pa Mlingo wopitilira 2 mg / kg, chilolezo chaulere kwaulere chinali 1 l / tsiku ndi T yomaliza_1/2 Masiku 6

Mapuloteni olemera kwambiri osagwiritsidwa ntchito ndi impso, chifukwa chake, impso excretion ya aflibercept ikuyembekezeka kukhala yochepera.

Linearity / nonlinearity of kuchotsa. Pokhudzana ndi chandamale chomangiriza cha aflibercept mpaka pa chandamale (amkati VEGF) free aflibercept pa Mlingo womwe uli pansipa 2 mg / kg udawonetsa kuchepa kwakanthawi (kosagwirizana ndi mzere) kuzungulira kwazinthu za kayendedwe ka kayendedwe kazinthu, zomwe zikuwoneka kuti zimagwirizanitsidwa ndi mgwirizano wake wapamwamba womwe umamangirira anthu amkati VEGF. Muli kuchuluka kuchokera pa 2 mpaka 9 mg / kg, chilolezo chaulere chimakhala chokhala ngati mzere, mwachidziwikire chifukwa cha njira zosakwanira zotere, monga protein catabolism.

Magulu apadera a odwala

Ana. Ndi pa / pakubweretsa mankhwala Zaltrap ® mu Mlingo wa 2, 2,5, 3 mg / kg pakapita masabata awiri aliwonse. Odwala 8 a ana odwala zotupa zolimba (azaka 5 mpaka 17), pafupifupi T_1/2 aflibercept yaulere, yotsimikiziridwa pambuyo pa mlingo woyamba, inali pafupifupi masiku 4 (masiku atatu mpaka 6).

Odwala okalamba. Zaka sizimakhudza ma pharmacokinetics a aflibercept.

Okwatirana Ngakhale pali kusiyana pakumasulidwa kwaulere ndi ma V_d mwa amuna ndi akazi, kusiyana pakati pa amuna ndi akazi munjira zake zowonekera bwino sikunawonedwe pakagwiritsidwa ntchito pa 4 mg / kg.

Mlozera wamasamba ambiri. Kuchuluka kwa thupi kunakhudza chidziwitso cha ufulu waulere ndi V_d Chifukwa chake, mwa odwala omwe ali ndi thupi loposa 100 makilogalamu, kuwonjezeka kwazinthu zomwe zimachitika pang'onopang'ono zimawonedwa ndi 29%.

Kuyanjana ndi mitundu. Mitundu ndi mafuko sizinakhudze ma pharmacokinetics a aflibercept.

Kulephera kwa chiwindi. Kafukufuku wokhudza kugwiritsa ntchito Zaltrap ® kwa odwala omwe ali ndi vuto la chiwindi sanachitike.

Odwala omwe ali ndi chidwi kwambiri (kuchuluka kwa bilirubin m'magazi ≤1.5 VGN paliponse pa zochitika za ACT) komanso sing'anga (kuchuluka kwa bilirubin m'magazi> 1.5-3 VGN pazotsatira zilizonse za ACT), kulephera kwa chiwindi sikunasinthe pakubwera kwachidziwitso kwa aflibercept . Palibe chidziwitso pa pharmacokinetics cha aflibercept mwa odwala omwe amawonongeka kwambiri kwa hepatic (kuchuluka kwa bilirubin m'magazi> 3 VGN pazinthu zilizonse za ACT).

Kulephera kwina. Kafukufuku wokhudza kugwiritsa ntchito Zaltrap ® kwa odwala omwe ali ndi vuto la impso sanachitike.

Palibe kusiyana komwe kunapezeka paziwonetsero zaulere (AUC) zaulere kwa odwala omwe amalephera kupweteka pogwiritsa ntchito ziphuphu zosiyanasiyana za Zaltrap ® pa 4 mg / kg.

Mimba komanso kuyamwa

Palibe zambiri pakugwiritsa ntchito kwa amayi apakati. Kafukufuku wazinyama adawulula zotsatira za embryotoxic and teratogenic atlibercept. Popeza angiogenesis ndiyofunikira kwambiri pakukula kwa mluza, kulepheretsa kwa angiogeneis mothandizidwa ndi Zaltrap ® kumatha kubweretsa mavuto. Kugwiritsa ntchito kwa Zaltrap ® pa nthawi yapakati komanso mwa amayi omwe angakhale ndi pakati sikulimbikitsidwa.

Amayi azaka zoyambira kubereka azilangizidwa kuti apewe kutenga pakati pa mankhwala ndi Zaltrap ®, ndipo ayenera kudziwitsidwa za kuthekera kwa zovuta zoyipa za Zaltrap ® pa mwana wosabadwayo.

Amayi azaka zoyambira kubereka komanso abambo achonde ayenera kugwiritsa ntchito njira zabwino za kulera panthawi yopereka mankhwala ngakhale kwa miyezi isanu ndi umodzi atatha kumwa mankhwala.

Pali kuthekera kwa chonde kwa abambo ndi amayi munthawi yamankhwala

Kafukufuku wa zamankhwala kuti athe kuwunika momwe Zaltrap ® imapangidwira mkaka wa m'mawere, kumasulidwa kwa aflibercept mkaka wa m'mawere ndi momwe zimakhudzira makanda sanachitike.

Sizikudziwika ngati aflibercept adachotsedwa mkaka wa m'mawere. Komabe, chifukwa chakuti sizingatheke kupatula kuthekera kolowera mkaka wa m'mawere, komanso mwayi wokhala ndi zovuta zoyipa zomwe zimayambitsidwa chifukwa chotsatira mwa makanda, ndikofunikira kukana kuyamwitsa kapena kusagwiritsa ntchito Zaltrap ® (kutengera kufunikira kwa kugwiritsa ntchito mankhwalawa mayi.

Zotsatira zoyipa

Zotsatira zoyipa zomwe zimachitika kawirikawiri (HP) (zamitundu yonse yazovuta, zamafupa ≥20%), zimawonetsedwa pafupifupi 2% nthawi zambiri mukamagwiritsa ntchito mankhwala a chemotherapy regimen Zaltrap ® /FOLFIRIkuposa mankhwala a chemotherapy FOLFIRIanali a HP otsatirawa (pofuna kuchepetsa kufala): leukopenia, kutsekula m'mimba, neutropenia, proteinuria, kuchuluka kwa machitidwe a ACT, stomatitis, kutopa, thrombocytopenia, kuchuluka kwa ntchito za ALT, kuthamanga magazi, kuchepa thupi, kuchepa kudya, kuchepa kwa magazi, kupweteka m'mimba, dysphonia, kuchuluka kwa seramu creatinine ndende ndi mutu.

HP yodziwika kwambiri ya digiri ya 3-4 degree (yokhala ndi ≥5%), imawonedwa pafupipafupi 2% nthawi zambiri mukamagwiritsa ntchito mankhwala a chemotherapy Zaltrap ® /FOLFIRI poyerekeza ndi regimen chemotherapy FOLFIRIanali HP wotsatira (pakuchepa kwa zochitika): neutropenia, kutsegula m'mimba, kuthamanga kwa magazi, leukopenia, stomatitis, kutopa, proteinuria ndi asthenia.

Mwambiri, kusiya kwa mankhwalawa chifukwa cha zovuta zomwe zachitika (zama degree onse azovuta) zinaonedwa mu 26.8% ya odwala omwe amalandila chemotherapy regimen Zaltrap ® /FOLFIRI, poyerekeza ndi 12.1% ya odwala omwe amalandila chemotherapy regimens FOLFIRI. HP yodziwika bwino kwambiri, yomwe idakhala chifukwa chokana mankhwala ≥1% ya odwala omwe adalandira chemotherapy regimen Zaltrap ® /FOLFIRIanali: asthenia / kutopa, matenda, kutsegula m'mimba, kuchepa magazi, kuchuluka kwa magazi, stomatitis, venous thromboembolic zovuta, neutropenia ndi proteinuria.

Kusintha kwa mankhwala Zaltrap ® (kuchepetsa kumwa ndi / kapena zosiyidwa) kunachitika mu 16,7%. Chithandizo cha zozungulira zotsatila zamankhwala zopitilira masiku 7 zinaonedwa mu 59.7% ya odwala omwe amalandila chemotherapy regimen Zaltrap ® /FOLFIRIpoyerekeza ndi 42.6% ya odwala omwe amalandila mankhwala a chemotherapy FOLFIRI.

Imfa ya zifukwa zina, kuwonjezera pa kudwala kwamatenda, omwe amawonekera mkati mwa masiku 30 pambuyo pa gawo lomaliza la chemotherapeutic regimen, idalembedwa mu 2.6% ya odwala omwe amalandila chemotherapy regimen Zaltrap ® /FOLFIRI, ndipo 1% ya odwala omwe amalandila chemotherapy regimen FOLFIRI. Choyambitsa imfa cha odwala omwe amalandila chemotherapy regimen Zaltra ® /FOLFIRIanali: matenda (kuphatikizapo neutropenic sepsis) mwa 4 odwala, kuchepa kwa madzi mu 2 odwala, hypovolemia mu 1 wodwala, metabolic encephalopathy mu 1 wodwala, kupuma thirakiti matenda (pachimake kupuma kulephera, chibayo ndi pulmonary embolism) 3 odwala, kusokonezeka kwa m'mimba thirakiti (kutuluka magazi kuchokera pachilonda cham'mimba, kutupa kwam'mimba, kuthina kwamatumbo kwathunthu) mwa odwala 3, kufa pazifukwa zosadziwika mu 2 odwala.

Pansipa pali HP ndi zonyansa zama laboratori zomwe zimawonetsedwa mu odwala omwe amalandila chemotherapy regimen Zaltrap ® /FOLFIRI ndi magawikidwe awo m'magulu a dongosolo mogwirizana ndi gulu la Medical Dictionary yoyang'anira zochitika MedDRA.

Ma HP omwe aperekedwa pansipa adatanthauzidwa ngati zovuta zilizonse zachipatala kapena zodwala mu ma labotale okhala ndi ≥2% pafupipafupi (kwa HP ya magawo onse azovuta) m'gululi lodziyerekeza ndi gulu la placebo mu kafukufuku wopangidwa mwa odwala omwe ali ndi ICP. Mphamvu ya HP idayikidwa malinga ndi NCI CTC (National Cancer Institute Common terminology MilanduUS National Cancer Institute General Toxicity Rating Scale) mtundu wa 3.0.

Zowopsa za HP zimatsimikiziridwa malinga ndi gulu la WHO motere: nthawi zambiri - ≥10%, nthawi zambiri - ≥1- incl. ≥3 zovuta).

Mbali ya magazi ndi zamitsempha yamagazi: Nthawi zambiri - leukopenia (wa magawo onse azovuta, kuphatikiza madigiri ≥3 a kuzunzika), neutropenia (ya magawo onse azovuta, kuphatikiza madigiri ≥3 a zovuta), thrombocytopenia (madigiri onse azovuta), nthawi zambiri - febrile neutropenia (ya magawo onse azovuta, kuphatikiza madigiri degree3 mwamphamvu), thrombocytopenia (≥3 digiri yakuopsa).

Kuchokera ku chitetezo chamthupi: Nthawi zambiri - Hypersensitivity zimachitika (madigiri onse azovuta), infrequently - hypersensitivity reaction (≥3rd zovuta).

Matenda a Metabolic ndi zakudya: pafupipafupi - kuchepa kwa njala (madigiri onse azovuta), nthawi zambiri - kuchepa kwa madzi m'thupi (madigiri onse azovuta zakuya komanso ≥3 degree), kuchepa kwa chilimbikitso (degree3 digiri yakuya).

Kuchokera ku dongosolo lamanjenje: Nthawi zambiri - mutu (wa madigiri onse azovuta), nthawi zambiri - kupweteka kwam'mutu ()3 digiri yayikulu), modabwitsa - POP.

Kuchokera pazombo: Nthawi zambiri - kuwonjezeka kwa kuthamanga kwa magazi (madigiri onse azovuta) (mu 54% ya odwala omwe anali ndi kuchuluka kwa kuthamanga kwa magazi (madigiri of3), kuwonjezeka kwa kuthamanga kwa magazi komwe kumachitika m'zaka ziwiri zoyambirira zamankhwala), magazi / kuchepa kwa magazi (kwamisempha yonse yamphamvu), Kutulutsa kofala kwambiri kunali ma mphuno zazing'ono (1-2 zovuta), zomwe nthawi zambiri zimakhala zovuta (ATEO) (monga pachimake ndimatenda amisala, kuphatikizaponso kuchepa kwa mtima wamisala, isina pectoris, intracardiac t mafupa, myocardial infarction, ochepa thromboembolism ndi ischemic colitis) (madigiri onse azovuta zamkati), venous thromboembolic complication (kwambiri vein thrombosis ndi pulmonary embolism) madigiri onse azovuta, magazi (≥3 digiri yakuopsa, nthawi zina yopha) - kutulutsa magazi m'mimba, hematuria, magazi pambuyo pa njira zachipatala, mafupipafupi samadziwika - mwa odwala omwe alandila Zaltrap ®, kukulira kwa hemorrhage kwambiri kwa hemorrhage ndi pulmonary hemorrhage / hemoptysis, i.e. . zakupha.

Kuchokera pakapumidwe, m'chifuwa ndi ziwalo zam'mimba: pafupipafupi - kufupika kwa mpweya (wa madigiri onse azovuta), mphuno (zamitundu yonse yamphamvu), dysphonia (ya magawo onse azovuta), nthawi zambiri - kupweteka kwa oropharynx (madigiri onse azovuta), rhinorrhea (rhinorrhea yokhawo kuwopsa kwa 1-2 , pafupipafupi - kupuma movutikira (≥3 digiri yakuya), mphuno zamkati (≥3 digiri yakuopsa), dysphonia (≥3 digiri yakuopsa), kupweteka kwa oropharynx (≥3 digiri yakuuma).

Kuchokera m'mimba: Nthawi zambiri - matenda otsegula m'mimba (kuphatikiza konse kwazovuta kuphatikiza 33 kuzungulira), stomatitis (yamavuto onse, kupweteka kwambiri), kupweteka kwam'mimba (kwa madigiri onse osautsa), kupweteka chapamwamba pamimba (madigiri onse azovuta), nthawi zambiri - kupweteka kwam'mimba ≥3 madigiri, kupweteka kwam'mimba (≥3 digiri yakuya), zotupa za m'mimba (kuthamanga konsekonse), magazi ochokera ku rectum (madigiri onse azovuta) , kupweteka kwa rectum (madigiri onse azakhungu), kupweteka kwameno (madigiri onse azovuta), aphthous stomatitis (madigiri onse azovuta), zithunzi fistulas (anal, matumbo ang'ono-kwamkodzo, kunja kwamkati wamatumbo (khungu laling'ono lamkati), matumbo akulu-kwamkati, matumbo milingo yovuta, kuphatikiza madigiri ≥3 a kupsinjika), kuphatikiza kunenepa kwa makoma am'mimba, kutuluka kwa magazi kuchokera ku rectum (≥3 digiri yakuya), aphthous stomatitis (≥3 digiri yakuuma), kupweteka kwa rectum ( ≥3 zovuta).

Pa khungu ndi subcutaneous minofu: pafupipafupi - kanjedza cham'madzi erythrodysesthesia syndrome (madigiri onse azovuta), nthawi zambiri - khungu hyperpigmentation (madigiri onse azovuta), palmar-plantar erythrodysesthesia syndrome (kukula kwa palm3).

Kuchokera ku impso ndi kwamkodzo thirakiti: Nthawi zambiri - proteinuria (malinga ndi kuchuluka kophatikizika kwa matenda ndi ma labotale) (madigiri onse azovuta), kuchuluka kwa serum creatinine ndende (madigiri onse azovuta), nthawi zambiri - proteinuria (≥3 degree of the severity), infrequently - nephrotic syndrome. Wodwala m'modzi wokhala ndi proteinuria ndikuwonjezera kuthamanga kwa magazi kuchokera kwa 611 odwala omwe amathandizidwa ndi chemotherapy regimen Zaltrap ® /FOLFIRI, adapezeka kuti ali ndi thrombotic microangiopathy.

Zovuta zamtundu uliwonse ndi zomwe zimachitika pamalo opangira jakisoni: Nthawi zambiri - zochitika za asthenic (madigiri onse azovuta), kumva kutopa (madigiri onse azovuta, kuphatikiza madigiri ≥3), kawirikawiri - zofunikira za vel3 (madigiri ≥3 kuzunza), koperewera - kuwonongeka kwa mabala kusiyanasiyana kwa m'mbali mwa bala, kulephera kwa anastomoses) (madigiri onse azovuta, kuphatikiza madigiri ≥3 mwamphamvu).

Zambiri zasayansi: Nthawi zambiri - kuchuluka kwa ntchito ya ACT, ALT (madigiri onse azovuta), kutsika kwamphamvu thupi (magawo onse azovuta), nthawi zambiri - ntchito yowonjezera ya ACT, ALT (≥3rd degree ya zovuta), kuchepa kwa thupi (madigiri ≥3) .

Pafupipafupi HP pamagulu apadera a odwala

Ukalamba. Odwala okalamba (≥ zaka 65), kuchuluka kwa matenda otsegula m'mimba, chizungulire, asthenia, kuchepa thupi komanso kuchepa thupi kunaposa 5% kuposa odwala omwe ali ndi zaka zochepa. Odwala okalamba ayenera kuyang'aniridwa bwino ndi matenda otsegula m'mimba komanso / kapena kuchepa kwamadzi.

Kulephera kwina. Odwala omwe ali ndi vuto lofooka la impso panthawi yoyambira kugwiritsa ntchito Zaltrap ®, zochitika za HP zinali zofanana ndi zomwe zimachitika mu odwala omwe sankagwira ntchito yaimpso panthawi yoyambira kugwiritsa ntchito Zaltrap ®. Odwala omwe ali ndi vuto lowonongeka komanso aimpso, kupezeka kwa sanali aimpso HP nthawi zambiri kuyerekeza ndi zomwe zimachitika mwa odwala popanda kulephera kwaimpso, kupatula kwa 10% yowonjezera madzi m'thupi (madigiri onse azovuta).

Immunogenicity Monga mankhwala ena onse okhala ndi mapuloteni, aflibercept ingakhale ndi chiopsezo cha immunogenicity.Mwambiri, malinga ndi zotsatira za mayeso onse a oncological, palibe wodwala aliyense yemwe adawonetsa chitetezo champhamvu kwambiri.

Kugwiritsa ntchito malonda pambuyo

Kuchokera pamtima: pafupipafupi osadziwika - kulephera kwa mtima, kuchepa kwa kachigawo kakang'ono ka mnofu wamanzere.

Kuchokera kumbali ya minofu ndi mafupa ophatikizika: pafupipafupi osadziwika - osteonecrosis ya nsagwada. Odwala omwe atenga mankhwala obzala pambuyo, milandu ya nsagwada ya mankhwalawa imanenedwa, makamaka kwa odwala omwe ali ndi chiopsezo cha nsagwada wa mankhwalawa, monga kugwiritsira ntchito bisphosphonates ndi / kapena njira zowukira zamano.

Mlingo ndi makonzedwe

Iv, mu mawonekedwe a kulowetsedwa kwa ola limodzi ndikutsatiridwa ndikuyambitsa kwa chemotherapeutic regimen FOLFIRI. Mlingo wovomerezeka wa Zaltrap ®, wogwiritsidwa ntchito limodzi ndi chemotherapeutic regimen FOLFIRIndi 4 mg / kg.

Chemotherapy regimen FOLFIRI

Pa tsiku loyamba la kuzungulira - munthawi yomweyo iv kulowetsedwa kudzera m'mitsempha ya Yinotecan pa mlingo wa 180 mg / m 2 kwa 90 min ndi calcium folinate (kumanzere- ndi kumanzere kwamanja) pamwala wa 400 mg / m 2 kwa 2 h, s pambuyo iv (bolus) makonzedwe a fluorouracil pa 400 mg / m 2, kenako kulowetsedwa kosalekeza kulowetsedwa kwa fluorouracil pa mlingo wa 2400 mg / m 2 kwa maola 46

Zozungulira za chemotherapy zimabwerezedwa sabata iliyonse iliyonse.

Kuchiza ndi Zaltrap ® kuyenera kupitirira mpaka matenda atakula kapena kukulira kawopsedwe wosavomerezeka.

Malangizo pakuwongolera dosing regimen / kuchedwa kwa chithandizo

Kuchiza ndi Zaltrap ® kuyenera kusiyidwa pazochitika zotsatirazi:

- kukula kwa magazi kwambiri,

- kukulitsa kukonzanso kwa makhoma am'mimba,

- Kukula kwa vuto la matenda oopsa kapena matenda oopsa a m'mimba,

- Kukula kwa zovuta za thromboembolic,

- kukula kwa nephrotic syndrome kapena thrombotic microangiopathy,

- kukula kwambiri hypersensitivity zimachitika (kuphatikizapo bronchospasm, kufupika kwa mpweya, angioedema, anaphylaxis),

- kuphwanya machiritso a mabala, omwe amafunikira chithandizo chamankhwala,

- Kukhazikika kwa kusintha kosinthika kwaposachedwa ka m'mimba posterhalopathy (POPs), komwe kumatchedwanso posterior leukoencephalopathy (POPs).

Osachepera milungu 4 ntchito isanachitike, chithandizo ndi Zaltrap ® chiyenera kuyimitsidwa kwakanthawi.

Kuti mumve zambiri za kuwonongeka kwa irinotecan, fluorouracil ndi calcium calcium, onani malangizo omwe angagwiritsidwe ntchito.

Magulu apadera a odwala

Ana. Chitetezo ndikuwoneka bwino kwa odwala mwa ana sichinakhazikitsidwe.

Pakufufuza ndi kulekerera ndi kuchuluka kwa mlingo, odwala 21 azaka za pakati pa 2 mpaka 21 (amatanthauza zaka 12,9 zaka) okhala ndi zotupa zolimba adalandira Zaltrap ® mu Mlingo wa 2 mpaka 3 mg / kg iv pakatha milungu iwiri iliyonse. Madongosolo a Pharmacokinetic a free aflibercept adayesedwa mwa 8 mwa odwalawa (wazaka 5 mpaka 17) onani Pharmacokinetics, kagawo kakang'ono "Magulu apadera odwala". Mlingo wolekereredwa kwambiri mu phunziroli anali mlingo wa 2,5 mg / kg, womwe unali wotsika kuposa mlingo wotetezeka komanso wogwira ntchito kwa achikulire omwe ali ndi khansa ya metastatic colorectal.

Odwala okalamba. Odwala okalamba safuna kusintha kwa mlingo wa Zaltrap ®.

Kulephera kwa chiwindi. Kafukufuku wokhudza kugwiritsa ntchito Zaltrap ® kwa odwala omwe ali ndi vuto la chiwindi sanachitike. Kutengera ndi manambala a kachipatala, kuwonekera kwazomwe zimachitika mwa odwala omwe ali ndi vuto lochepa kwambiri la chiwindi kunali kofanana ndi kwa odwala omwe ali ndi chiwindi chokwanira.

Umboni wamankhwala umafotokoza kuti kusintha kwa mankhwalawa kwa odwala omwe ali ndi kufatsa pang'ono komanso kosafunikira sikufunika.

Palibe chidziwitso pakugwiritsa ntchito aflibercept kwa odwala omwe ali ndi chiwindi cha hepatic.

Kulephera kwina. Kafukufuku wokhudza kugwiritsa ntchito Zaltrap ® kwa odwala omwe ali ndi vuto laimpso sanachitike. Kutengera ndi manambala a kachipatala, kuwonekera kwatsatanetsatane kwa odwala omwe ali ofatsa pang'ono pang'ono aimpso kunali kofanana ndi kwa odwala omwe ali ndi vuto laimpso.

Umboni wamankhwala umati kuwongolera koyamba kwa mankhwala ofunikira kwa odwala omwe ali ndi kufatsa kwaimpso sikofunikira. Pali chidziwitso chochepa kwambiri pakugwiritsa ntchito mankhwalawa kwa odwala omwe amalephera kwambiri aimpso, choncho muyenera kusamala mukamagwiritsa ntchito mankhwalawa.

Malangizo pokonzekera mayankho ndi mawu ake

Mankhwala ayenera kugwiritsidwa ntchito moyang'aniridwa ndi dokotala wodziwa kugwiritsa ntchito mankhwala a antitumor.

Osaba kubaya. Osalowetsa iv mu jet (osathamanga komanso osakwiya).

Zaltrap ® sicholinga cha makonzedwe amkati.

Monga momwe amakonzera makolo onse, asanakonze, yankho la Zaltrap ® liyenera kuyang'aniridwa bwino kuti pakhale tizinthu tating'onoting'ono kapena tinthu tina tating'onoting'ono.

Diluted Zaltrap ® zothetsera ziyenera kuyendetsedwa pogwiritsa ntchito kulowetsedwa kwa IV komwe kumapangidwa ndi PVC yomwe imakhala ndi diethylhexyl phthalate (DEHP), PVC yopanda DEHP, koma yomwe ili ndi trioctyltrimellate (TOTM), polypropylene, PE, yophimbidwa mkati mwa PVC, polyurethane.

Zida za kulowetsedwa kwa IV ziyenera kukhala ndi zosefera za polyethersulfone zokhala ndi mainchesi a pore a 0,2. Osagwiritsa ntchito polyvinylidene fluoride (PVDF) kapena zosefera za nayiloni.

Chifukwa cha kusowa kwa maphunziro othandizira, Zaltrap ® sayenera kusakanikirana ndi mankhwala ena kapena sol sol, kupatula 0.9% sodium chloride solution ndi 5% dextrose solution.

Kukonzekera kwa kulowetsedwa ndikutsatira

Njira yothetsera kulowetsedwa kwa mankhwala a Zaltrap ® iyenera kukonzedwa ndi katswiri wazachipatala potsatira njira zoyenera zotetezedwa.

Osagwiritsa ntchito botolo limodzi ndi mankhwalawo ngati njira yokhazikika yokhala ndi tinthu tosatulutsa kapena ngati pali kusintha kwa mtundu wake.

Z kulowetsedwa zopangidwa kuchokera ku PVC zokhala ndi DEHP kapena polyolefin (yopanda PVC ndi DEHF) ziyenera kugwiritsidwa ntchito.

Zokhudza kulowetsedwa kwa mtsempha chifukwa cha hyperosmolarity (1000 mosmol / kg) ya Zaltrap ® concentrate.

Mankhwalawa sanapangire jakisoni kulowa m'thupi la vitreous.

Kuzungulira kwa mankhwala a Zaltrap ® kuyenera kuchepetsedwa. Chotsani kuchuluka kwa Zaltrap ® yokhazikika ndikuwonjezera pa voliyumu yofunikira ndi 0.9% sodium chloride yankho la jakisoni kapena 5% dextrose yankho la jakisoni.

Kuzunzika kwa aflibercept mu kulowetsedwa njira yothetsera kulowetsedwa kwa Zaltrap ® kuyenera kukhala kosiyanasiyana 0,6-8 mg / ml.

Kuchokera pamalingaliro azinthu zopanda pake, yankho losungunuka la Zaltrap ® liyenera kugwiritsidwa ntchito nthawi yomweyo, kukhazikika kwake kwa thupi ndi mankhwala kumakhalabe mpaka maola 24 pa kutentha kwa 2-8 ° C ndi mpaka maola 8 pa kutentha kwa 25 ° C.

Mbale za mankhwala a Zaltrap ® zimapangidwa kuti azigwiritsa ntchito limodzi. Mankhwala aliwonse osagwiritsidwa ntchito omwe atsalira mu vial ayenera kutayidwa malinga ndi zofunikira zaku Russia. Osabowolanso cholembera cham'mbuyo pambuyo poti singano yangaikapo kale.

Bongo

Palibe zambiri zokhudzana ndi chitetezo cha kutenga Zaltrap ® mu Mlingo wopitilira 7 mg / kg kamodzi pa masabata awiri kapena 9 mg / kg kamodzi sabata iliyonse.

Zizindikiro HP yodziwika bwino kwambiri ndi mankhwalawa a dosing anali ofanana ndi HP yomwe idawonedwa ndi mankhwala othandizira.

Chithandizo: kukonza mankhwala amafunikira, makamaka kuwunika ndi kuchiza kuchuluka kwa kuthamanga kwa magazi ndi proteinuria. Palibe mankhwala enieni a Zaltrap ®. Wodwala amayenera kuyang'aniridwa ndi achipatala kuti azindikire ndi kuwunikira aliyense amene akufotokozedwa mu gawo la "Zotsatira zoyipa".

Kutulutsa Fomu

Tsatirani njira yothetsera kulowetsedwa, 25 mg / ml. 4 ml ya mankhwalawa mu botolo lagalasi lopanda utoto (mtundu wa I), wokhathamira ndi cholembera cha mphira wa brkidutyl wokhala ndi cholembera cha aluminium crimp ndi mphete yomata komanso chosindikizira chidindo. 1 kapena 3 fl. pa kakhadi kadi. 8 ml ya mankhwalawa mu botolo lagalasi lopanda utoto (mtundu I), wokhathamira ndi cholembera cha mphira wa brkidutyl wokhala ndi cholembera cha aluminium crimp ndi mphete yomata komanso chosindikizira chidindo. 1 fl. pa kakhadi kadi.

Malangizo ogwiritsira ntchito Zaltrap

Chithandizo: aflibercept 25 mg
Othandizira: sodium phosphate monohydrate (E339), sodium hydrogen phosphate heptahydrate (E339), citric acid monohydrate (E330), sodium citrate dihydrate (E331), granular sodium chloride, sucrose, Polysorbate 20 (E433), hydrochloric acid 36% (E507 hydrohlide). (E524), madzi a jakisoni.
Kufotokozera Transparent colorless kapena wotumbululuka chikasu madzi, wopanda zonyansa zazitsulo.

Kufotokozera zamankhwala

Mankhwala ndi a gulu la antitumor othandizira. Zimapangidwa mokhazikika, komwe njira zothetsera zimakonzedwera. Dzinalo losavomerezeka padziko lonse lapansi ndi loyenera. Mayina amalonda ndi Zaltrap ndi Eilea.

Zizindikiro zogwiritsidwa ntchito

Nthawi yomweyo, mlingo wina wa folic acid, irinotecan ndi fluorouracil amatengedwa. Zinthu zonsezi zimagwiritsidwa ntchito ngati chemotherapy mwa odwala omwe ali ndi khansa ya colorectal, pomwe amawonetsa kukana kwakukulu ndi othandizira ena a antitumor. Komanso, "Zaltrap" imagwiritsidwa ntchito pobwezeretsanso.

Pharmacological zochita za aflibercept

Mothandizidwa ndi aflibercept, ma receptor omwe amapereka mapangidwe amitsempha yatsopano yamafuta azakudya ndikuthandizira kukula kwa chotupa kusiya kugwira ntchito. Chifukwa chakuti magazi osakwanira, magaziwo amachepa pang'onopang'ono, maselo a atypical amasiya kugawikana ndikukula.

Zambiri za momwe metabolism ya mapuloteni a aflibercept zimachitikira sapezeka. Asayansi amati limagawikana ndi ma amino acid ndi ma peptide. Yogwiritsa ntchito imachotsedwa m'thupi kwa masiku asanu ndi limodzi ndi ndowe. Impso sizitenga nawo mbali popereka ndalama.

Malangizo ogwiritsira ntchito "Zaltrap"

Mankhwalawa amalowetsedwa m'mitsempha kwa ola limodzi. Mlingo amawerengedwa pa 4 mg pa kilogalamu ya kulemera kwa thupi. Dongosolo la chemotherapeutic likhala motere:

1. Patsiku loyamba la mankhwalawa, mugwiritsa ntchito mawonekedwe a Y-catheter, mothandizidwa ndi kulowetsedwa kwamitsempha imagwiritsidwa ntchito limodzi ndi irinotecan muyezo wa 180 mg pa mita lalikulu. Ndondomeko kumatenga mphindi 90. Calcium calcium amaperekera kwa maola awiri pa mulingo wa 400 mg ndi kuchuluka komweko kwa fluorouracil,
2. Kulowetsedwa kotsatira kudzakhala kopitilira kwa maola 46. Pankhaniyi, fluorouracil amatumizidwa mu Mlingo wa 2400 mg.

Kuzungulira kwa mankhwalawa kumachitika mobwerezabwereza milungu iwiri iliyonse. Kwa anthu omwe ali ndi matenda ashuga, mulingo wofunikira suyenera kusinthidwa.

Kulowetsedwa kuyenera kuchitika ndi dokotala yemwe akudziwa za chemotherapeutic mazoezi.

Mwa mawonekedwe osakhazikika komanso mwa jet, mankhwalawa sayenera kuperekedwa kulikonse.

Musanagwiritse ntchito, yankho limayang'aniridwa mosamala. Iyenera kukhala yowoneka bwino popanda ma particles osasungunuka.

Osagwiritsa ntchito zida zakufa za nylon kapena polyvinylidene fluoride pa infusions.

Popeza palibe chidziwitso pakuphatikizidwa kwa mankhwalawa ndi mankhwala ena, kuphatikiza kwa thunthu lokha ndi yankho la sodium chloride kapena dextrose ndikuloledwa.

Dokotala yekha ndiye ayenera kukonza yankho la kulowetsedwa kwa mtsempha, kutsatira malamulo a asepisi. Osagwiritsa ntchito botolo lomwe lili ndi tinthu tosasinthika kapena mtundu wa mankhwalawo wasintha. Pambuyo kuchepetsedwa, kuchuluka kwa aflibercept kuyenera kukhala m'chigawo cha 0.6-8 mg / ml. Ndikofunikira kugwiritsa ntchito mankhwala omalizidwa nthawi yomweyo, chifukwa kuteteza kukhazikika kwa thupi ndi mankhwala kumatha kuchitika masana okha.

Kuli kuti ndibwino kugula "Zaltrap", mtengo wake ndi chosungira

Mutha kugula mankhwala ku pharmacy. Kuti muchite izi, muyenera kupereka malangizo a dokotala. Popanda iyo, kugulitsa mankhwalawa sikuphatikizidwa. Mtengo wa botolo la mankhwala umachokera ku ma ruble 8500.

Mankhwalawa ayenera kukhala m'chipinda momwe kutentha sikokwanira kuposa 8 osati kutsika kuposa 2 degrees. Mankhwalawa sayenera kuwonekera pakayendedwe ka dzuwa.

Mutha kusunga mankhwalawo kwa zaka zitatu kuyambira tsiku lopangidwa. Nthawi ikatha, simungathe kugwiritsa ntchito mankhwalawa, chifukwa chake ayenera kutayidwa.

Ndemanga za "Zaltrap"

"Saltrap" adasamalira abambo anga. Awa ndi mankhwala abwino, amagwira ntchito molimbana ndi chotupacho, koma mavuto nthawi zonse amapezeka. Ndibwino kuti muzipaka jakisoni kamodzi pakatha milungu iwiri, chifukwa abambo anali ovuta kwambiri kulolera chemotherapy. Koma kuwunika kunawonetsa kuti neoplasm ikuchepa.

Pambuyo pa kukhazikitsidwa kwa "Zaltrap" ndimakhala ndimmutu nthawi zambiri, nseru komanso kusanza, ndimakhala ndikufuna kugona. Koma mankhwalawa amakhudza chotupa mwachangu kwambiri. Chifukwa chake, kuti mupeze zotsatira zabwino, mutha kupirira.

Ngakhale mankhwalawa ndiokwera mtengo kwambiri ndipo mawonekedwe ake pambuyo poipa, koma amathandiza. Mothandizidwa ndi maphunziro angapo, ndinatha kuchotsa chotupacho. Madotolo akuti pali mwayi pang'ono wobwereranso. Ndisanalandire mankhwalawa, ndimathandizidwa ndi ena, koma zotsatira zake zidapitilira kwakanthawi. Pambuyo pa Zaltrap, sindinakhalepo ndi zizindikiro za khansa kwa zaka zingapo.

Tidzakhala okondwa kwambiri ngati mungachiwongolere ndikugawana nawo pamagulu ochezera

Kutulutsa mafomu ndi kapangidwe kake

Gwiritsani ntchito njira yothetsera kulowetsedwa. Mbale zokhala ndi kuchuluka kwa 4 ml ndi 8 ml. Kuchuluka kwazinthu zazikuluzikulu za aflibercept ndi 25 mg mu 1 ml. Njira yachiwiri ndi njira yokhazikika yopanda njira yovomerezeka yolumikizira mafupa. Mtundu wa yankho ndi wowonekera kapena wowala wachikasu.

Chofunikira kwambiri ndi mapuloteni otsegulika. Omwe amathandizira: sodium phosphate, citric acid, hydrochloric acid, sucrose, sodium chloride, sodium hydroxide, madzi.

Aflibercept imalepheretsa ntchito ya ma receptors, omwe amachititsa kuti mitsempha yatsopano ya magazi idyetse chotupacho ndikuthandizira kukula kwambiri. Kutsalira popanda magazi, neoplasm imayamba kuchepa kukula. Ndondomeko ya kukula ndikugawika kwa maselo ake atypical amasiya.

Aflibercept imalepheretsa zochitika za ma receptors, omwe amachititsa kuti mitsempha ya magazi ipangike.

Ndi chisamaliro

Kuwunikira nthawi zonse zaumoyo wa odwala omwe ali ndi vuto la impso, ochepa matenda oopsa, matenda a mtima, komanso magawo oyamba a kulephera kwa mtima kumafunika. Mochenjera, mankhwalawa amaperekedwa kwa odwala okalamba komanso odwala omwe ali ndi vuto lathanzi, ngati mulingo wotsika sikhala wapamwamba kuposa 2 point.

Momwe mungatenge Zaltrap?

Intravenous makonzedwe - kulowetsedwa kwa 1 ora. Mlingo wamba ndi 4 mg pa kilogalamu ya kulemera kwa thupi. Chithandizo chimasainidwa pamaziko a chemotherapeutic regimen:

• tsiku loyamba la mankhwala: kulowetsedwa kudzera mu mawonekedwe a Y-otupa a Irinotecan 180 mg / m, kwa mphindi 90, calcium imayamwa kwa mphindi 120 pa mlingo wa 400 mg / m² ndi 400 mg / m² Fluorouracil,
• kulowetsedwa kosatha kumatenga maola 46 ndi mulingo wa Fluorouracil 2400 mg / m².

Intravenous makonzedwe - kulowetsedwa kwa 1 ora.

Amazungulira masiku 14 aliwonse.

Matumbo

Kutsegula m'mimba, kupweteka kwam'mimba kwa zinthu zingapo zazikulu, kukula kwa zotupa, mapangidwe a fistulas mu anus, chikhodzodzo, matumbo ochepa. Kupweteka kwameno, kupweteka kwam'mimba, kupweteka kwa rectum, nyini. Fistulas m'mimba yogaya ndi kukonza makoma sizichitika kawirikawiri, zomwe zingayambitse kuti wodwalayo afe.

Zizindikiro zoyipa za kupuma: dyspnea nthawi zambiri imachitika.

Kuchokera pamtima

Amalumphira kuthamanga kwa magazi, kutulutsa magazi mkati. Odwala ambiri: thromboembolism, ischemic attack, angina pectoris, chiwopsezo chachikulu cha kulowerera myocardial. Pafupipafupi: kutsegula kwa magazi m'mimba, kukhetsa magazi, kutulutsa magazi m'matumbo am'mimba, omwe akupha.

Zokhudza mphamvu pakuwongolera njira

Palibe zambiri pa kafukufuku wazomwe zimachitika chifukwa cha mankhwalawa. Ndikulimbikitsidwa kuti musayendetse ntchito ndikugwiritsa ntchito njira zovuta ngati wodwalayo ali ndi zovuta kuchokera ku dongosolo lamkati lamanjenje, matenda a psychomotor.

Pamasamba azithandizo zatsopano (masiku 14 aliwonse), kuyezetsa magazi kuyenera kuchitidwa.

Pamasamba azithandizo zatsopano (masiku 14 aliwonse), kuyezetsa magazi kuyenera kuchitidwa. Mankhwala chikuyendetsedwera mu chipatala kukhazikitsidwa munthawi yochepa zizindikiro za kuchepa magazi, mafuta a makoma am'mimba thirakiti.

Odwala omwe ali ndi chidziwitso chazachipatala cha 2 paki kapena kuposa apo ali ndi chiopsezo cha zotsatila. Amafuna kuyang'aniridwa ndi achipatala pafupipafupi kuti azindikire kuwonongeka kwakanthawi paumoyo.

Kapangidwe ka fistulas mosasamala kanthu komwe akukhala ndi chizindikiro cha kutha kwa chithandizo. Sizoletsedwa kugwiritsa ntchito mankhwalawa pochiza odwala omwe adachitidwa opaleshoni yayikulu (mpaka mabala amachira kwathunthu).

Amuna ndi akazi a msinkhu wobereka ayenera kugwiritsa ntchito njira zosiyanasiyana zakulera asanakwanitse miyezi isanu ndi umodzi (osachepera) atatha kumwa mankhwala a Zaltrap. mimba ya mwana siyenera kupatula.

Zaltrap yankho ndi hyperosmotic. Kapangidwe kake sikumagwiritsa ntchito mankhwalawa kwa intraocular space. Sizoletsedwa kuyambitsa yankho mu thupi la vitreous.

Gwiritsani ntchito mu ukalamba

Pali chiopsezo chachikulu chotenga matenda otsegula m'mimba, chizungulire, kuchepa thupi komanso kuchepa madzi m'thupi mwa odwala omwe ali ndi zaka 65 ndi akulu. Mankhwala a Saltrap ayenera kuchitika pokhapokha poyang'aniridwa ndi ogwira ntchito kuchipatala. Pachizindikiro choyamba cha kutsegula m'mimba kapena kusowa kwamadzi, chithandizo chamankhwala chofunikira chimafunikira.

Mankhwala a Saltrap ayenera kuchitika pokhapokha poyang'aniridwa ndi ogwira ntchito kuchipatala.

Gwiritsani ntchito pa nthawi yoyembekezera komanso mkaka wa m`mawere

Zambiri pakugwiritsa ntchito Zaltrap mwa amayi apakati komanso oyamwitsa sapezeka.

Popeza kuopsa kwa zotsatira zoyipa kwa mwana, mankhwala a antitumor samayikidwa m'magulu a odwala.

Zambiri zokhudzana ndi momwe gawo la mankhwala limayamwa mkaka wa m'mawere siili. Ngati ndi kotheka, ntchito mankhwala mankhwalawa khansa kwa mayi woyamwitsa, mkaka wa m`mawere ayenera anathetsedwa.

Wopanga

Sanofi-Aventis Deutschland GmbH, Germany.

Tumor mankhwala

Zotsatira za Antitumor a Mavitamini

Ksenia, wazaka 55, ku Moscow: “Maphunziro a Zaltrap adawerengedwa kwa abambo anga kuti amuchiritse khansa. Mankhwalawa ndi abwino, ogwira ntchito, koma ovuta kwambiri. Nthawi zonse pamakhala zizindikiro zoyipa. Ndikwabwino kuti amathandizidwa kamodzi pakatha masabata awiri aliwonse, chifukwa pambuyo pa chemotherapy mkhalidwe wa abambo umangokulirakulira kwakanthawi, koma mayesowo adawonetsa njira yabwino yochepetsera vuto la neoplasm. ”

Eugene, wazaka 38, Astana: “Ndinali ndi mavuto ambiri kuchokera ku Zaltrap. Vutoli linali loyipa chabe: kusanza, kusanza, kupweteka mutu pafupipafupi, kufooka kwambiri. Koma mankhwalawo amagwira ntchito pachotupa msanga. Zotsatira zake pakugwiritsa ntchito mankhwalawa khansa ndiyenera kupulumuka chizunzo chonsechi. "

Alina, wazaka 49, Kemerovo: "Awa ndi mankhwala okwera mtengo, ndipo matendawa atalandira mankhwala enaake ndiwakuti sindikufuna kukhala ndi moyo. Koma ndi othandiza. Mu 1 kumene, chotupa changa chinatsala pang'ono kutha. Dotolo adati pali mwayi woti ubwezeretsanso, koma ochepa. Mankhwala ena adagwiritsidwa ntchito Zaltrap isanakwane, koma matendawo anali osakhalitsa, ndipo nditakhala zaka zitatu osakhala ndi vuto la khansa. "

Zaltrap jekeseni

Musanayambe kumwa mankhwalawa, uzani dokotala wanu za mankhwala omwe agwiritsidwa kale ntchito, mavitamini othandizira kudya (mwachitsanzo, mavitamini, zowonjezera zachilengedwe, ndi zina), zovuta zomwe zimachitika, matenda omwe alipo, komanso zikhalidwe zamakono zathanzi (mwachitsanzo, kutenga pakati, opaleshoni yomwe ikubwera, ndi zina zambiri).

Zotsatira zoyipa za mankhwalawa zimatha kutchulidwa mthupi lanu. Tengani mankhwalawo monga momwe dokotala wakupangirani kapena tsatirani malangizo ogwiritsira ntchito mankhwalawo. Mlingo wa mankhwalawa zimatengera momwe mulili. Uzani dokotala wanu ngati palibe chosintha kapena vuto lanu likuipiraipira.

Mfundo zofunika kukambirana ndi wopereka chithandizo chaumoyo zalembedwa pansipa.

• Yang'anirani mosamala odwala okalamba ndi kutsegula m'mimba

Dziwani zambiri: Njira zopewera komanso malamulo ogwiritsira ntchito

Kuti mupeze izi, chonde funsani kwa asing'anga, akatswiri a zamankhwala kapena werengani zambiri pazomwe zimapangidwa.

Zaltrap Injectable ikupezeka m'mapaketi otsatirawa ndi zotsatirazi mwamphamvu

Ma CD a Zaltrap Osungidwa: 4MG

Mankhwalawa amapangidwa ndi makampani otsatirawa

Kodi chololedwa kugwiritsa ntchito zida zamafakitale kwambiri pomamwa mankhwalawa? Ngati mukumva kugona, chizungulire, hypotension, kapena kupweteka m'mutu mukutenga Zaltrap Injectable, ndiye kuti mungafunike kusiya kuyendetsa galimoto ndi zida zamaofesi.

Muyenera kusiya kuyendetsa galimoto ngati kumwa mankhwalawo kumakupangitsani kugona, kuzizira, kapena kuyambitsa chidwi. Madokotala amalimbikitsa kusiya kumwa mowa ndi mankhwalawa, chifukwa mowa umalimbitsa kwambiri mavuto komanso kugona. Chonde onani zotsatira izi mthupi lanu mukamagwiritsa ntchito Zaltrap Injectable.

Onetsetsani kuti mwawonana ndi dokotala kuti akuthandizeni kuganiziranso za thupi lanu komanso thanzi lanu lonse. Kodi mankhwalawa (mankhwala) ndi osokoneza bongo kapena osokoneza bongo? Mankhwala ambiri sachita mankhwala osokoneza bongo kapena osokoneza bongo.

Nthawi zambiri, boma limagawaniza mankhwala omwe amatha kukhala osokoneza bongo ngati mankhwala otulutsidwa. Mwachitsanzo, graph H kapena X ku India ndi graph II-V ku USA. Chonde werengani zambiri zomwe zakupaka mankhwalawa kuti mutsimikizire kuti mankhwalawo saikidwa m'manja.

Kuphatikiza apo, musamayeserere komanso musazolowere thupi lanu kulandira mankhwala popanda kufunsa dokotala. Kodi ndizotheka kusiya kumwa nthawi yomweyo, kapena ndikufunika kuchepetsa pang'onopang'ono? Mankhwala ena amayenera kutha pang'onopang'ono chifukwa cha kuchira kwake.

Onetsetsani kuti mwawonana ndi dokotala kuti akuthandizeni kuganizira za thupi lanu, thanzi lanu lonse komanso mankhwala ena omwe mukumwa.

Ngati mwaphonya mlingo wotsatira, tengani mwachangu. Ngati nthawi yotsatila ikuyandikira, mutha kudumpha nthawi yomwe mwapangana ndikupitiliza kutsatira ndondomeko yanu yanthawi zonse. Osamamwa mlingo wowonjezereka kuti mupange mlingo womwe wakuphonya.

Ngati mukukumana ndi izi pafupipafupi, lingalirani kukhazikitsa zikumbutso kapena pemphani wina wa banja lanu kuti azisunga nthawi.

Onetsetsani kuti mukumana ndi dokotala kuti musinthe dongosolo kuti mulandire chithandizo chomwe mwaphonya (ngati mutaphonya masiku angapo).

Musapitirire mlingo woyenera. Kugwiritsa ntchito mankhwala mopitilira muyeso sikungachepetse mkhalidwe wanu, komanso kungayambitse poyizoni ndi zovuta zoyipa. Ngati mukudziwa za mankhwala osokoneza bongo a Zaltrap Injectable, lemberanani ndi a emergency, chipatala kapena chipatala chapafupi kwambiri.

Onetsetsani kuti mwabweretsa ma CD, chidebe kapena dzina la mankhwala kuti mupeze matenda. Osapitilira mankhwala anu kwa anthu ena, ngakhale atakhala ofanana ndi inu, kapena zikuwoneka kuti matendawa ali ndi zizindikiro zingapo, chifukwa izi zimatha kuyambitsa bongo.

• Sungani kukonzekera kwa firiji, m'malo ozizira komanso kutali ndi dzuwa. Osamazizira kukonzekera ngati lamulo lotere silikuperekedwa mwachindunji m'malangizo. Sungani mankhwala kutali ndi zinyama ndi ana.

  Musamakololere kuchimbudzi kapena m mene madyekeramo ngati izi sizinafotokozedwe mwachindunji. Mankhwala otayidwa mwanjira imeneyi amatha kuvulaza chilengedwe.

  Kuti mumve zambiri za kutaya kwa Zaltrap Injectable, funsani omwe amakuthandizani pazaumoyo.

Ngakhale mlingo umodzi wa Zaltrap womwe utatha ntchito umatha kubweretsa mavuto. Onetsetsani kuti mwawonana ndi dokotala ngati mukumva kufooka kapena kuwawa. Kuphatikiza apo, mankhwala omwe atha ntchito amatha kulephera kugwira ntchito yake polimbana ndi matenda anu.

Kuti muwonetsetse chitetezo chanu, ndikofunikira kwambiri kukana kumwa mankhwala omwe adatha.

Ngati mukudwala matenda omwe amafunikira chithandizo chanthawi zonse (matenda amtima, kupweteka, mapangidwe osokoneza), muyenera kukhazikitsa njira yolumikizirana ndi wogulitsa mankhwala kuti muzikhala ndi mankhwala atsopano omwe ali ndi moyo wabwinoko.

Chonde funsani kwa dokotala kapena wamankhwala, ndikuwonanso zambiri zomwe zili pamapulogalamu.

1. LABEL yojambulidwa tsiku ndi tsiku: ZALTRAP-ziv-aflibercept solution, gwiritsani ntchito https://dailymed.nlm.nih.gov/dailymed/dr ...... - Apeza: October 12, 2016.
2. Zisankho za NHS. Ndichite chiyani ngati ndaphonya mtundu wa maantibayotiki? - Adapeza: Julayi 14, 2016.
3. Kodi Mwalandiridwapo Dwala Lanu? - Adapeza: Julayi 3, 2016.
4. Cancer.Net (2014).

Kufunika kotenga mankhwala anu moyenera - Kufikika: Julayi 3, 2016.