Inotuzumab
Jeneng merek: Besponsa
Kelas obat:
Agen Antineoplastik
Panganggone Inotuzumab
Prekursor Sel B Leukemia Limfoblastik Akut
Pengobatan kambuh utawa refrakter sel B prekursor leukemia limfoblastik akut (pra-B-ALL) (ditunjuk minangka obat yatim piatu dening FDA kanggo perawatan pra-B- ALL).
Efficacy ditemtokake adhedhasar remisi lengkap (CR) lan remisi lengkap karo Recovery hematologic incomplete (CRi) ing open-label, sinau phase 3 acak (INO-VATE ALL) ing pasien karo kambuh utawa refraktori pra-B-ALL.
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Carane nggunakake Inotuzumab
Umum
Distribusi Watesan
Administrasi
IV Administrasi
Kanggo informasi kompatibilitas solusi, deleng Kompatibilitas ing Stabilitas.
Administrasi kanthi infus IV. Produsen nyaranake poliolefin, PVC (diethylhexylphthalate [DEHP] utawa non-DEHP), utawa administrasi polybutadiena kanthi utawa tanpa saringan. Yen saringan digunakake, nggunakake polyethersulfone (PES) -, polyvinylidene fluoride (PVDF) -, utawa polysulfone hidrofilik (HPS) - Filter adhedhasar; aja nganggo saringan nilon utawa campuran ester selulosa (MCE).
Kudu direkonstitusi lan diencerake sadurunge administrasi. Gunakake sajrone 8 jam sawise rekonstitusi (kalebu wektu infus). (Waca Panyimpenan ing Stabilitas.)
ReconstitutionReconstitute vial ngemot 0,9 mg inotuzumab ozogamicin karo 4 mL banyu steril kanggo injeksi kanggo nyedhiyani solusi ngemot 0,25 mg/mL. Alon-alon swirl vial. Aja goyangake solusi reconstituted.
Larutan reconstituted kudu bening nganti opalescent, ora ana warna nganti rada kuning, lan bebas saka partikel sing katon.
PengenceranEncerake dosis sing cocog ing PVC (DEHP utawa non -DEHP), poliolefin, utawa tas infus etilena vinil asetat (EVA) sing ngemot injeksi natrium klorida 0,9% kanggo entuk volume total 50 mL. Nyampur solusi sing diencerke kanthi inversi sing lembut; aja goyang.
Tarif AdministrasiDiwenehake kanthi infus IV kanthi laju 50 mL/jam sajrone 1 jam.
Dosis
Dewasa
Prekursor Sel B Leukemia Limfoblastik Akut IVSiklus 1: 0,8 mg / m2 ing dina 1, banjur 0,5 mg / m2 ing dina 8 lan 15 sajrone siklus 3 minggu. Bisa nambah durasi siklus nganti 4 minggu yen CR utawa CRi diraih lan/utawa kedadeyan keracunan.
Siklus sakteruse ing pasien sing durung entuk CR utawa CRi: 0,8 mg/m2 ing dina 1, banjur 0,5 mg / m2 ing dina 8 lan 15 sajrone saben siklus 4 minggu. Mungkasi obat yen CR utawa CRi ora digayuh sajrone 3 siklus.
Siklus sakteruse ing pasien sing wis entuk CR utawa CRi: 0,5 mg/m2 ing dina 1, 8, lan 15 sajrone saben siklus 4 minggu.
Durasi terapi ngirim ora ngluwihi 6 siklus ing pasien sing ora bakal ngalami HSCT. Ing pasien sing ngalami HSCT sawise terapi inotuzumab ozogamicin, durasi terapi sing disaranake yaiku 2 siklus; Nanging, bisa uga nimbang siklus katelu yen CR utawa CRi lan minimal residual disease (MRD) negatif ora digayuh ing 2 siklus pisanan (siklus 1-2). (Deleng Hepatotoksisitas, kalebu VOD Hepatik, ing Ati-ati.)
Modifikasi Dosis kanggo ToksisitasAja nambah maneh dosis sawise nyuda dosis kanggo keracunan.
Toksisitas Hematologic IVPenundaan dosis bisa uga dibutuhake. yen ANC lan jumlah trombosit durung pulih menyang nilai sing disaranake sadurunge miwiti siklus perawatan anyar; penundaan dosis sajrone siklus perawatan (yaiku, dina 8 lan/utawa 15) ora perlu.
Kanggo ANC <1000/mm3 ing pasien sing duwe ANC baseline ≥1000/mm3, tundha siklus sabanjure nganti ANC ≥1000/mm3. Yen neutropenia sing gegandhengan karo perawatan sing dawa (yaiku, tahan> 28 dina), mandhegake obat kasebut.
Kanggo jumlah trombosit <50.000/mm3 ing pasien sing duwe jumlah trombosit awal ≥50.000/mm3, tundha siklus sabanjure. nganti jumlah trombosit ≥50.000/mm3. Yen trombositopenia sing gegandhengan karo perawatan sing dawa (yaiku, luwih saka 28 dina), mandhegake obat kasebut.
Yen neutropenia utawa trombositopenia dumadi ing pasien sing duwe ANC awal <1000/mm3 lan/utawa jumlah trombosit <50.000/ mm3, tundha siklus sabanjure nganti salah siji saka ing ngisor iki: ANC lan jumlah trombosit bali menyang paling sethithik nilai awal, ANC ≥1000/mm3 lan jumlah trombosit ≥50.000/mm3, utawa penilaian sumsum balung nuduhake penyakit sing stabil utawa apik lan neutropenia lan trombositopenia dianggep gegandhengan karo penyakit.
Hepatotoksisitas IVKanggo konsentrasi ALT lan/utawa AST serum> 2,5 kaping ULN utawa total konsentrasi bilirubin> 1,5 kaping ULN (kajaba ing pasien sindrom Gilbert utawa hemolisis), interupsi terapi nganti ALT lan AST pulih dadi ≤2,5 kaping ULN lan total konsentrasi bilirubin pulih dadi ≤1,5 kaping ULN. Yen terapi ditahan nganti <7 dina, dosis sabanjure ditindakake sawise resolusi keracunan; Nanging, nyetel jadwal administrasi kanggo njaga minimal 6 dina antarane dosis. Yen terapi ditahan kanggo ≥7 dina nanging <14 dina, ngilangi dosis sabanjure. Yen terapi ditahan nganti ≥14 dina, nyuda dosis nganti 25% ing siklus sabanjure; yen perlu ngurangi dosis luwih, ngurangi frekuensi administrasi ing siklus sakteruse saka 3 kanggo 2 dosis saben siklus. Yen modifikasi dosis (ngurangi dosis utawa frekuensi suda) ora ditoleransi utawa konsentrasi ALT, AST, utawa total bilirubin mundhak nganti> 28 dina sanajan terapi dihentikan, mandhegake obat kasebut kanthi permanen.
Yen VOD ati utawa liyane abot. hepatotoksisitas kedadeyan, mandhegake obat kanthi permanen.
Reaksi sing gegandhengan karo infus IVYen reaksi sing gegandhengan karo infus kedadeyan, interupsi infus utawa mandhegake obat kanthi permanen lan gawe perawatan lan perawatan sing cocog. Gumantung saka keruwetan (kajaba reaksi sing abot utawa sing ngancam nyawa), bisa uga nimbang mandhegake infus utawa nerusake infus lan administrasi kortikosteroid lan antihistamin.
Yen reaksi sing ana hubungane karo infus sing abot utawa ngancam nyawa, mungkasi obat kanthi permanen.
Toksisitas Nonhematologic Liyane IVKanggo keracunan nonhematologis kelas 2 utawa luwih (kajaba kanggo hepatotoksisitas lan efek sing gegandhengan karo infus), interupsi terapi nganti keracunan bali menyang awal utawa nambah menyang kelas 1. Yen terapi ditahan kanggo <7 dina, ngatur dosis sabanjure sawise resolusi keracunan; Nanging, nyetel jadwal administrasi kanggo njaga minimal 6 dina antarane dosis. Yen terapi ditahan kanggo ≥7 dina nanging <14 dina, ngilangi dosis sabanjure. Yen terapi ditahan nganti ≥14 dina, nyuda dosis nganti 25% ing siklus sabanjure; yen perlu ngurangi dosis luwih, ngurangi frekuensi inotuzumab ozogamicin ing siklus sakteruse saka 3 kanggo 2 dosis saben siklus. Yen modifikasi dosis (ngurangi dosis utawa nyuda frekuensi) ora ditoleransi utawa keracunan nonhematologis tetep nganti >28 dina sanajan terapi diganggu, mandhegake obat kanthi permanen.
Watesan Resep
Wong diwasa
Prekursor Sel B Leukemia Limfoblastik Akut IVDurasi terapi ngirim ora ngluwihi 6 siklus ing pasien sing ora bakal ngalami HSCT. Ing pasien sing ngalami HSCT sawise terapi inotuzumab ozogamicin, durasi terapi ora kudu ngluwihi 2 siklus; Nanging, bisa nimbang siklus katelu yen CR utawa CRi lan negativitas penyakit residual minimal ora digayuh ing 2 siklus pisanan (siklus 1-2). (Deleng Hepatotoksisitas, kalebu VOD Hepatik, ing Ati-ati.)
Populasi Khusus
Gangguan Hepatik
Konsentrasi ALT/AST serum ≤2,5 kaping ULN lan total bilirubin konsentrasi ≤1,5 kaping ULN: Ora ana pangaturan dosis awal sing dibutuhake. (Deleng Populasi Khusus miturut Farmakokinetik.)
Konsentrasi ALT/AST serum >2,5 kaping ULN lan/utawa total konsentrasi bilirubin >1,5 kaping ULN: Data winates; ora ana rekomendasi dosis spesifik.
Gagal ginjal
Clcr 15–89 mL/menit: Ora ana rekomendasi dosis spesifik. (Deleng Populasi Khusus miturut Farmakokinetik.)
Penyakit ginjel tahap pungkasan (kalebu sing nampa dialisis): Ora diteliti; ora ana rekomendasi dosis tartamtu ing wektu iki.
Pasien Geriatrik
Ora ana pangaturan dosis awal sing dibutuhake.
Pènget
Kontraindikasi
Pènget / PancegahanPènget
Hepatotoksisitas, kalebu VOD Hepatik
Hepatotoksisitas, kalebu VOD sing abot, ngancam nyawa, lan kadhangkala fatal (uga dikenal minangka sindrom obstruksi sinusoidal) lan kelainan tes fungsi ati, sing dilapurake ing pasien sing diobati inotuzumab ozogamicin. . Ing studi INO-VATE ALL, VOD hepatik dumadi luwih kerep ing pasien sing diobati inotuzumab ozogamicin sing ngalami terapi HSCT sawise obat kasebut tinimbang sing tanpa HSCT. Umume kasus VOD hepatik yaiku kelas 3 utawa luwih elek. Wektu rata-rata kanggo wiwitan VOD hepatik ing pasien sing ngalami HSCT: 15 dina (rentang: 3-57 dina). Antarane wong-wong sing ora ngalami HSCT, VOD hepatik dilapurake nganti 56 dina sawise dosis pungkasan obat kasebut utawa sajrone tindak lanjut.
Risiko VOD hepatik tambah ing pasien sing ngalami HSCT sawise terapi inotuzumab ozogamicin , sing nampa regimen kahanan sing ngemot 2 agen alkylating, lan sing konsentrasi total bilirubin paling anyar ana ing utawa ndhuwur ULN sadurunge HSCT. Faktor risiko liyane kalebu penyakit hepatik sing isih ana utawa sadurunge, riwayat HSCT, umur sing luwih tuwa, penyakit sing wis diobati banget (yaiku, terapi nylametake mengko), lan tambah akeh siklus perawatan karo inotuzumab ozogamicin. Pasien sing wis ngalami VOD sadurunge utawa sing duwe penyakit hepatik sing terus-terusan serius uga duwe risiko tambah akeh penyakit hepatik, kalebu pangembangan VOD, sawise terapi obat kasebut.
Ngurangi durasi perawatan nganti 2 siklus ing pasien. ngalami HSCT. (Deleng Prekursor Sel B Leukemia Limfoblastik Akut ing Dosis lan Administrasi.)
Sawetara ahli nyaranake administrasi obat bebarengan kayata ursodiol kanggo nyegah pangembangan VOD hepatik.
Ngawasi tandha-tandha kanthi rapet. lan gejala VOD hepatik (contone, konsentrasi total bilirubin sing dhuwur, hepatomegali, bobote cepet, asites, edema, jaundice).
Kaji tes fungsi ati (yaiku, ALT, AST, total bilirubin, alkali fosfatase) sadurunge lan sawise saben dosis inotuzumab ozogamicin; Kajaba iku, ngawasi kanthi teliti tes fungsi ati kanggo sasi kapisan sawise HSCT lan banjur kurang kerep sakwise, miturut praktik klinis standar.
Yen ana hepatotoksisitas, gangguan sauntara terapi, nyuda dosis, utawa mandheg obat bisa uga dibutuhake. . (Deleng Hepatotoksisitas ing Dosis lan Administrasi.)
Yen ana VOD hepatik, mandhegake obat kasebut kanthi permanen. Perawatan sing ndhukung, kalebu njaga keseimbangan cairan sing nyukupi, dianjurake dening sawetara ahli; administrasi terus ursodiol uga dianjurake. Natrium defibrotide bisa digunakake ing perawatan pasien karo VOD hepatik kanthi kompromi ginjel utawa paru-paru.
Tambah Resiko Kematian Non-kambuh Pasca-transplantasiTambah mortalitas ing dina 100 post-HSCT ing pasien sing ngalami HSCT sawise terapi inotuzumab ozogamicin. Panyebab paling umum saka kematian non-kambuh pasca-HSCT yaiku VOD hepatik lan komplikasi infèksius.
Ngawasi kanthi rapet kanggo manifestasi komplikasi pasca-HSCT, kalebu infeksi lan VOD hepatik. (Deleng Hepatotoksisitas, kalebu VOD Hepatik, ing Cautions.)
Pènget lan Pancegahan Liyane
MyelosuppressionNeutropenia lan trombositopenia, nyebabake komplikasi sing abot, ngancam nyawa, lan kadhangkala fatal (contone, pneumonia, sepsis neutropenia, sepsis, syok septik, sepsis pseudomonal, pendarahan), kacarita. Komplikasi infèksi sing ana gandhengane karo neutropenia asring kedadeyan. Perdarahan hemoragik sing paling umum yaiku epistaksis.
Pantau jumlah CBC sadurunge saben dosis.
Miwiti terapi anti-infektif profilaksis lan gunakake tes pengawasan sajrone terapi lan sawise terapi.
Pantau tandha lan gejala komplikasi sing gegandhengan karo myelosuppression (contone, infeksi, pendarahan). Yen neutropenia, trombositopenia, utawa komplikasi sing gegandhengan karo myelosuppression, gangguan sementara terapi, pengurangan dosis, utawa mandheg obat bisa uga dibutuhake. (Deleng Keracunan Hematologi ing Dosis lan Administrasi.)
Reaksi sing gegandhengan karo infusReaksi sing gegandhengan karo infus dilapurake, umume sakcepete sawise rampung infus sajrone siklus perawatan pisanan. Reaksi sing gegandhengan karo infus rampung kanthi spontan utawa sawise intervensi medis.
Premedikasi karo kortikosteroid, antipiretik, lan antihistamin sadurunge saben dosis.
Ngawasi kanthi rapet kanggo manifestasi reaksi sing gegandhengan karo infus (contone. , mriyang, ndredheg, ruam, kesulitan ambegan) sajrone lan ≥1 jam sawise rampung infus. Yen reaksi sing ana gandhengane karo infus kedadeyan, interupsi sauntara infus utawa mandheg obat kasebut bisa uga dibutuhake bebarengan karo perawatan sing cocog lan perawatan sing ndhukung. (Deleng Reaksi sing gegandhengan karo Infus ing Dosis lan Administrasi.)
Prolongation of QT IntervalProlongation of the QT interval report.
Gunakake kanthi ati-ati ing pasien kanthi riwayat utawa predisposisi kanggo prolongation. saka interval QTc, pasien kanthi bebarengan nampa obat liya sing dikenal bisa nambah interval QT, lan pasien kanthi kelainan elektrolit. (Deleng Obat sing ndawakake Interval QT ing Interaksi.)
Monitor ECG lan elektrolit serum sadurunge miwiti inotuzumab ozogamicin, sawise miwiti obat apa wae sing dikenal bisa nambah interval QTc, lan sacara periodik sajrone terapi kaya sing dituduhake sacara klinis. .
Morbiditas lan Mortalitas Janin/NeonatalAdhedhasar mekanisme tumindak lan temuan kewan, bisa nyebabake cilaka janin. Toksisitas embriofetal dituduhake ing kewan.
Verifikasi status meteng sadurunge miwiti terapi. Aja meteng sajrone terapi. Wanita sing duwe anak lan wong lanang sing dadi mitra wanita kasebut kudu nggunakake metode kontrasepsi sing efektif nalika nampa inotuzumab ozogamicin lan ≥8 lan ≥5 sasi, sawise obat kasebut mandheg.
Yen digunakake nalika meteng utawa pasien dadi meteng, ngandhani potensial bebaya janin.
Kerusakan KesuburanBisa ngrusak kesuburan lanang lan wadon.
ImunogenisitasKacarita Antibodi marang inotuzumab ozogamicin. Reresik ora kena pengaruh antibodi. Antibodi sing netralake ora dilapurake.
Populasi Tertentu
KandhutanBisa nyebabake cilaka janin. (Waca Fetal/Neonatal Morbidity and Mortality ing Cautions.)
Konfirmasi status meteng sadurunge miwiti terapi.
LaktasiOra dingerteni manawa inotuzumab ozogamicin utawa metabolite disebarake menyang susu. Efek ing bayi sing nyusoni lan produksi susu uga ora dingerteni. Aja nyusoni sajrone terapi lan nganti ≥2 sasi sawise mandheg obat.
Panggunaan PediatrikKeamanan lan khasiat durung ditetepake.
Panggunaan GeriatrikIng studi INO-VATE ALL, 18% saka pasien umure ≥65 taun. Ora ana bedane khasiat utawa safety relatif marang wong diwasa sing luwih enom sing diamati; Nanging, trombositopenia, neutropenia febrile, lan konsentrasi γ-glutamyltransferase (γ-glutamyltranspeptidase, GGT, GGTP) luwih kerep kedadeyan ing pasien geriatrik.
Umur tuwa digandhengake karo risiko ngembangake VOD ati ing pasien sing diobati inotuzumab ozogamicin. (Deleng Hepatotoksisitas, kalebu VOD Hepatik, ing Cautions.)
Farmakokinetik ora katon sacara substansial dipengaruhi dening umur pasien; pangaturan dosis awal ing pasien geriatrik ora perlu. (Deleng Populasi Khusus miturut Farmakokinetik.)
Gangguan HepatikReresik ora kena pengaruh saka gangguan hepatik entheng sing wis ana.
Data winates ing pasien kanthi gangguan hepatik moderat utawa abot sing wis ana; nanging, reresik ora katon suda. (Deleng Populasi Khusus miturut Farmakokinetik.)
Gagal GinjalReresik ora kena pengaruh gagal ginjal (Clcr 15–89 mL/menit). (Deleng Populasi Khusus miturut Farmakokinetik.)
Efikasi lan safety ing pasien penyakit ginjel tahap pungkasan (kanthi utawa tanpa hemodialisis) ora dingerteni.
Efek Samsaya Awon
Kambuh utawa refrakter ALL: Trombositopenia, neutropenia, infeksi, anemia, leukopenia, lemes, pendarahan, pyrexia, mual, sirah, neutropenia febrile, konsentrasi ALT lan/utawa AST munggah pangkat , nyeri abdomen, konsentrasi γ-glutamyltransferase meningkat, hiperbilirubinemia.
Apa obatan liyane bakal mengaruhi Inotuzumab
In vitro, N-acetyl-γ-calicheamicin dimethylhydrazide utamane dimetabolisme kanthi reduksi nonenzimatik. In vitro, inhibisi isoenzim CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, lan 3A4/5 lan isoenzim UGT 1A1, 1A4, 1A6, 1A9, lan 2B7 ora ana ing konsentrasi klinis sing relevan. In vitro, induksi isoenzim CYP 1A2, 2B6, lan 3A4 ora mungkin ing konsentrasi klinis sing relevan.
N-acetyl-γ-calicheamicin dimethylhydrazide minangka substrat saka P-glikoprotein (P-gp). Ora mungkin nyandhet P-gp, protein tahan kanker payudara (BCRP), transporter anion organik (OAT) 1 utawa OAT3, transporter kation organik (OCT) 2, lan protein transport anion organik (OATP) 1B1 lan OATP1B3.
In vitro, inotuzumab ozogamicin ora bisa nyandhet CYP isoenzim 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, lan 3A4/5 kanthi signifikan utawa ngindhuksi isoenzim CYP 1A2, 3A2, lan 3A46 sing relevan. >
Obat sing ndawakake Interval QT h3>
Bisa efek aditif ing QT didandani (QTc) -interval prolongation karo obatan dikenal kanggo ndawakake interval QT utawa nimbulaké torsades de pointes. Aja nggunakake bebarengan; mungkasi nggunakake obatan kuwi utawa nimbang nggunakake obatan alternatif tanpa potensial prolongation QT-interval. Yen panggunaan bebarengan ora bisa dihindari, monitor ECG lan konsentrasi elektrolit serum luwih kerep (yaiku, sadurunge miwiti terapi inotuzumab ozogamicin, sawise miwiti obat apa wae sing dikenal kanggo ndawakake interval QTc, lan sacara periodik sajrone terapi kaya sing dituduhake sacara klinis). (Deleng Prolongation of QT Interval ing Cautions.)
Obat Hepatotoksik
Amarga VOD hepatik lan kelainan tes fungsi ati digandhengake karo terapi inotuzumab ozogamicin, sawetara ahli nyaranake ngindhari terapi bebarengan karo obat liya. dikenal nyebabake hepatotoksisitas ing pasien sing nampa inotuzumab ozogamicin lan regimen kahanan dosis dhuwur kanthi agen alkilasi, yen bisa. (Deleng Hepatotoksisitas, kalebu VOD Hepatik, ing Awas.)
Obat Spesifik
Obat
Interaksi
Komentar
Agen alkylating (contone, Busulfan, melphalan, thiotepa)
Tambah risiko VOD hepatik ing pasien sing ngalami HSCT sawise terapi inotuzumab ozogamicin, kalebu sing nampa regimen kahanan sing ngemot 2 agen alkilasi (pirsani Hepatotoksisitas, kalebu VOD hepatik, miturut Awas)
Hindari regimen pengkondisian sing ngemot 2 agen alkilasi ing pasien sing ngalami HSCT sawise terapi inotuzumab ozogamicin
Anti jamur, azoles
Kamungkinan nambah risiko hepatotoksisitas
Sawetara ahli nyaranake ngindhari panggunaan bebarengan, yen bisa
Disclaimer
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