Dasatinib (Systemic)
Jeneng merek: Sprycel
Kelas obat:
Agen Antineoplastik
Panganggone Dasatinib (Systemic)
Leukemia Myelogenous Kronis (CML)
Pengobatan CML positif kromosom Philadelphia (Ph+) Philadelphia sing mentas didiagnosis ing wong diwasa sing ana ing fase kronis penyakit kasebut.
Pengobatan Ph+ CML ing wong diwasa sing ana ing krisis ledakan myeloid utawa limfoid, ing fase akselerasi, utawa ing fase kronis penyakit kasebut, sawise gagal (sekunder kanggo resistensi utawa intoleransi) saka terapi sadurunge kalebu Imatinib .
Pengobatan Ph+ CML ing pasien pediatrik ≥1 taun sing ana ing fase kronis penyakit kasebut.
Ditetepake obat yatim piatu dening FDA kanggo digunakake ing perawatan CML.
Leukemia Limfositik Akut (Lymphoblastic) (ALL)
Pengobatan Philadelphia chromosome-positive (Ph+) ALL ing wong diwasa sawise gagal (sekunder kanggo resistensi utawa intoleransi) saka terapi sadurunge.
Kanggo kombinasi karo kemoterapi kanggo perawatan Ph+ ALL sing mentas didiagnosis ing pasien pediatrik ≥1 taun.
Ditetepake obat yatim piatu dening FDA kanggo digunakake ing perawatan ALL akut.
Panganggone Liyane
Wis digunakake kanggo perawatan Noonan-syndrome† [off-label] sing ana gandhengane karo kardiomiopati hipertrofik. Ditunjuk minangka obat yatim piatu dening FDA kanggo digunakake ing kondisi iki.
Wis digunakake kanggo perawatan tumor stroma gastrointestinal (GIST)† [off-label].
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Carane nggunakake Dasatinib (Systemic)
Umum
Skrining Pretreatment
Ngawasi Pasien h4> Pasien Dewasa
Pangawasan Dispensing lan Administrasi
Penanganan lan PembuanganPertimbangan Umum Liyane
Administrasi
Administrasi Lisan
Administrasi lisan sapisan dina (esuk utawa sore) tanpa preduli dhaharan.
Administrasi ing wektu sing padha saben dina.
Nguntal tablet wutuh; aja ngethok, ngunyah, utawa ngremuk.
Yen dosis ora kejawab, njupuk dosis sabanjure ing wektu sing biasa. Aja njupuk rong dosis bebarengan.
Dosis
Pasien Anak
CML Fase Kronis Oral≥1 taun: Dosis adhedhasar bobot awak kaya sing diterangake ing Tabel 1. Ngitung maneh dosis saben 3 sasi utawa luwih kerep yen perlu kanggo ngitung owah-owahan bobot awak.
Dosis tablet ora dianjurake kanggo pasien bocah sing bobote <10 kg.
Tabel 1. Dosis Dasatinib ing Pasien Anak kanthi CML1 Fase KronisBobot Badan (kg)
Dosis Awal sing Disaranake
10 nganti <20
40 mg sapisan dina
20 nganti <30
60 mg sapisan dina
30 nganti <45
70 mg sapisan dina
≥45
100 mg sapisan dina
Ing pasien sing ora entuk respon hematologis utawa cytogenetic ing dosis awal sing disaranake, tambah dosis dasatinib kaya sing diterangake ing Tabel 2.
Tabel 2. Eskalasi Dosis Dasatinib ing Pasien Pediatrik kanthi Fase Kronis CML1Dosis Awal
Dosis Tambah
40 mg sapisan dina
50 mg sapisan dina
60 mg sapisan dina
70 mg sapisan dina
70 mg sapisan dina
90 mg sapisan dina
100 mg sapisan dina saben dina
120 mg sapisan dina
Paparan sistemik dasatinib sawise administrasi tablet dasatinib sing disebar ing jus 36% luwih murah tinimbang tablet utuh ing 5 pasien umur 2-10 taun kanthi Ph+ KABEH. Khasiat lan safety saka nyebarake tablet dasatinib durung ditetepake.
Terusake perawatan nganti bukti kemajuan penyakit utawa nganti ora ditoleransi maneh dening pasien.
Durasi terapi sing optimal durung ditemtokake kanthi jelas.
ALL Oral≥1 taun (ing kombinasi karo kemoterapi): Dosis adhedhasar bobot awak kaya sing diterangake ing Tabel 3. Recalculate dosis saben 3 sasi utawa luwih kerep yen perlu kanggo akun owah-owahan ing bobot awak . Terusake terapi nganti 2 taun.
Miwiti terapi ing utawa sadurunge dina 15 kemoterapi induksi. Eskalasi dosis ora dianjurake kanggo pediatrik Ph+ ALL amarga dasatinib diwenehake kanthi kombinasi karo kemoterapi.
Dosis tablet ora dianjurake kanggo pasien bocah sing bobote <10 kg.
Tabel 3. Dosis Dasatinib ing Pasien Pediatrik kanthi Ph+ ALL1Bobot Badan (kg)
Dosis Awal sing Disaranake
10 nganti <20
40 mg sapisan dina
20 nganti <30
60 mg sapisan dina
30 nganti <45
70 mg sapisan dina
≥45
100 mg sapisan dina
Paparan sistemik saka dasatinib sawise administrasi tablet dasatinib sing disebar ing jus 36% luwih murah tinimbang tablet utuh ing 5 pasien 2-10 taun. umur karo Ph + ALL. Khasiat lan safety saka nyebarake tablet dasatinib durung ditetepake.
Modifikasi Dosis Efek Saleh Nonhematologis OralYen ana reaksi salabetipun nonhematologis sing abot, tahan dasatinib nganti keracunan wis rampung utawa apik. Sawisé iku, nerusake terapi, yen cocok, ing dosis suda gumantung saka keruwetan awal acara.
Ing pasien pediatrik karo Ph+ ALL, sementara interupsi terapi yen kelas 2 keracunan nonhematologic dumadi; nalika keracunan nambah kanggo kelas 1 utawa kurang, nerusake therapy ing dosis asli utawa ngurangi dosis (sawise episode sakteruse) minangka diterangake ing Tabel 4. Yen kelas 3 keracunan nonhematologic occurs, therapy interrupt sementara; nalika keracunan mutusake kanggo kelas 1 utawa kurang, nerusake terapi kanthi dosis suda kaya sing diterangake ing Tabel 4.
Yen konsentrasi bilirubin langsung munggah > 5 kaping konsentrasi ULN utawa AST/ALT >15 kaping ULN kedadeyan, ngganggu terapi sementara; nalika keracunan mutusake menyang kelas 1 utawa kurang, nerusake terapi ing dosis asli utawa nyuda dosis (sawise episode sakteruse) kaya sing diterangake ing Tabel 4.
Tabel 4. Penyesuaian Dosis Dasatinib kanggo Toksisitas Nonhematologis ing Pasien Pediatrik1Original Dosis Awal
Pengurangan Dosis Setingkat
Pengurangan Dosis Dua Tingkat
40 mg
20 mg
Kekuwatan tablet sing luwih murah ora kasedhiya
60 mg
40 mg
20 mg
70 mg
60 mg
50 mg
100 mg
80 mg
70 mg
Efek Saleh Hematologis OralIng pasien ing fase kronis CML ngalami Neutropenia utawa thrombocytopenia kelas 3 utawa luwih sajrone respon hematologis lengkap, terapi sementara ditahan. Bisa nerusake terapi dasatinib kanthi dosis sing suda. Pengurangan dosis sauntara bisa uga perlu kanggo tingkat neutropenia lan trombositopenia lan respon penyakit.
Ing pasien karo Ph+ ALL sing ngalami neutropenia utawa trombositopenia sing terus-terusan (>3 minggu) sing ora ana hubungane karo ALL (kaya sing ditemtokake dening aspirasi sumsum balung utawa biopsi). Perawatan bisa diterusake kanthi dosis wiwitan asli utawa kanthi dosis suda kaya sing diterangake ing Tabel 5 nalika ANC mutusake nganti ≥1000/mm3 lan jumlah trombosit mudhun dadi ≥75,000/mm3. Yen neutropenia utawa thrombocytopenia kambuh, baleni aspirasi sumsum balung utawa biopsi lan nerusake dasatinib kanthi dosis suda (Tabel 5). Yen neutropenia lan / utawa thrombocytopenia tundha siklus sabanjure luwih saka 14 dina, ngganggu terapi dasatinib lan diterusake kanthi dosis sing padha sawise siklus sabanjure diwiwiti. Yen neutropenia lan / utawa thrombocytopenia tetep lan siklus sabanjure luwih telat nganti 7 dina, nglakoni penilaian sumsum balung kanggo netepake seluleritas lan persentase jeblugan. Yen selularitas sumsum balung <10%, interupsi perawatan karo dasatinib nganti ANC> 500/mm3. Yen neutropenia lan / utawa thrombocytopenia kambuh lan tundha siklus sabanjure nganti 7 dina, baleni aspirasi sumsum balung utawa biopsi. Yen selularitas sumsum kurang saka 10%, perawatan bisa diterusake kanthi dosis lengkap yen ANC ngluwihi 500/mm3. Yen selularitas sumsum balung luwih saka 10%, coba nerusake terapi.
Tabel 5. Penyesuaian Dosis Dasatinib kanggo Neutropenia utawa Thrombocytopenia ing Pasien Anak karo Ph+ ALL1Dosis Awal Asli
Satu tingkat Pengurangan Dosis
Pengurangan Dosis rong tingkat
40 mg
20 mg
Kekuwatan tablet sing luwih murah ora kasedhiya
60 mg
40 mg
20 mg
70 mg
60 mg
50 mg
100 mg
80 mg
70 mg
Dewasa
CML Fase Kronis Oral100 mg sapisan dina. Yen respon hematologi utawa cytogenetic ora digayuh, tambahake dosis nganti 140 mg sapisan dina.
Terusake perawatan nganti bukti kemajuan penyakit utawa nganti ora ditoleransi maneh dening pasien.
Durasi terapi optimal durung ditemtokake kanthi jelas.
Fase Akselerasi utawa Krisis Blast Oral140 mg sapisan dina. Yen respon hematologis utawa cytogenetic ora digayuh, tambahake dosis nganti 180 mg sapisan dina.
Terusake perawatan nganti bukti kemajuan penyakit utawa nganti ora ditoleransi maneh dening pasien.
Durasi optimal saka perawatan. terapi durung ditetepake kanthi jelas.
ALL Oral140 mg sapisan dina. Yen respon hematologis utawa cytogenetic ora digayuh, tambahake dosis nganti 180 mg sapisan dina.
Terusake perawatan nganti bukti kemajuan penyakit utawa nganti ora ditoleransi maneh dening pasien.
Durasi optimal saka perawatan. terapi durung ditetepake kanthi jelas.
Modifikasi Dosis kanggo Keracunan Efek Saleh Nonhematologis OralYen reaksi salabetipun nonhematologis sing abot, nahan dasatinib nganti keracunan wis rampung utawa apik. Sawisé iku, nerusake terapi, yen cocok, ing dosis suda gumantung saka keruwetan awal saka acara.
Efek Hematologis sing Saleh OralInterupsi sauntara, nyuda dosis, utawa mandheg dituduhake ing pasien sing ngalami neutropenia abot lan/utawa trombositopenia (pirsani Tabel 6 lan 7). Faktor pertumbuhan hematopoietik wis digunakake ing pasien kanthi myelosupresi tahan.
Tabel 6. Fase Kronis CML: Penyesuaian Dosis kanggo Neutropenia lan Thrombocytopenia1Dosis Awal
Episode Neutropenia utawa Thrombocytopenia (Pengukuran Hematologis)
Panyesuaian Dosis
100 mg sapisan dina
Episode pisanan (ANC <500/mm3 utawa trombosit < 50.000/mm3)
Nahan dasatinib; bisa diterusake kanthi dosis asli (100 mg sapisan dina) yen ANC tekan ≥1000/mm3 lan trombosit tekan ≥50.000/mm3 sajrone 7 dina
Episode kapindho (ANC <500/mm3 tahan >7 dina utawa trombosit < 25.000/mm3)
Nahan dasatinib; bisa diterusake kanthi dosis suda 80 mg sapisan dina nalika ANC tekan ≥1000/mm3 lan trombosit tekan ≥50.000/mm3
Episode katelu (ANC <500/mm3 tahan >7 dina utawa trombosit <25.000/mm3)
Pasien sing nampa dasatinib kanggo penyakit sing mentas didiagnosis: Nahan dasatinib; bisa diterusake kanthi dosis suda 50 mg sapisan dina nalika ANC tekan ≥1000/mm3 lan trombosit tekan ≥50.000/mm3
Pasien sing nampa dasatinib sawise gagal terapi sadurunge: Mungkasi obat
Tabel 7. Dipercepat Phase utawa Blast Phase CML lan Ph+ ALL: Penyesuaian Dosis kanggo Neutropenia lan Thrombocytopenia1Dosis Awal
Pengukuran Hematologi
Panyesuaian Dosis
140 mg sapisan dina
ANC <500/mm3 utawa trombosit <10.000 /mm3
1. Yen sitopenia ora ana hubungane karo leukemia (kaya sing ditemtokake dening aspirasi sumsum utawa biopsi), mandhegake dasatinib nganti ANC ≥1000/mm3 lan trombosit ≥20.000/mm3
2. Diterusake perawatan kanthi dosis asli (140 mg sapisan dina)
3. Yen kambuh ANC <500/mm3 utawa trombosit <10.000/mm3 ana, baleni langkah 1 lan nerusake terapi kanthi dosis suda 100 mg sapisan dina (sawise episode kapindho) utawa 80 mg sapisan dina (sawise episode katelu)
p>4. Yen sitopenia ana hubungane karo leukemia (kaya sing ditemtokake dening aspirasi sumsum utawa biopsi), tambahake dosis nganti 180 mg sapisan dina
Populasi Khusus
Gangguan Hepatik
Ora Rekomendasi dosis khusus ing wektu iki.
Genal Gagal
Saiki ora ana rekomendasi dosis khusus.
Pasien Geriatri
Saiki ora ana rekomendasi dosis khusus.
Pènget
Kontraindikasi
Pènget/PanandhapEfek Hematologis
Myelosuppression (utamane neutropenia abot, anemia, lan trombositopenia) umume kedadeyan lan biasane bisa dibalik; luwih kerep ing pasien ing fase akselerasi utawa blast CML lan ing sing duwe Ph + ALL tinimbang ing pasien ing fase kronis CML.
Penundaan sementara terapi utawa pengurangan dosis bisa uga dibutuhake yen keracunan hematologis kedadeyan.
Ing pasien karo CML fase kronis, nindakake CBC saben 2 minggu sajrone terapi 3 wulan pisanan lan banjur saben 3 sasi (utawa kaya sing dituduhake sacara klinis). Ing pasien kanthi CML fase advance utawa Ph+ ALL, nindakake CBC saben minggu sajrone terapi 2 wulan pisanan lan saben wulan (utawa kaya sing dituduhake sacara klinis).
Ing pasien pediatrik kanthi Ph+ ALL, nindakake CBC sadurunge wiwitan saben blok kemoterapi lan minangka indikasi klinis; sajrone blok konsolidasi kemoterapi, nindakake CBC saben 2 dina nganti pulih.
Pendarahan
Risiko pendarahan abot, kalebu pendarahan SSP utawa GI sing bisa fatal; biasane digandhengake karo trombositopenia sing abot.
Pendarahan sing abot bisa uga mbutuhake interupsi perawatan lan transfusi.
Gunakake kanthi ati-ati ing pasien sing nampa antikoagulan utawa obat sing nyegah fungsi trombosit.
Retensi Cairan
Risiko retensi cairan sing abot (yaiku, efusi pleura, efusi perikardial, edema paru, asites, edema umum).
Retensi cairan umume dikelola kanthi perawatan sing ndhukung (contone, diuretik, kursus singkat saka kortikosteroid).
Evaluasi gejala sing nuduhake efusi pleura utawa retensi cairan liyane (contone, dyspnea anyar utawa saya tambah nalika aktifitas utawa istirahat, batuk garing, nyeri dada pleuritik) kanthi dada radiograf. Efusi pleura sing abot bisa mbutuhake thoracentesis lan terapi oksigen. Coba nyuda dosis utawa interupsi terapi yen ana retensi cairan.
Efek Jantung
Bisa nyebabake disfungsi jantung utawa prolongation saka interval QT.
Gunakake kanthi ati-ati ing pasien sing duwe utawa bisa ngalami prolongation saka interval QT (contone, hypokalemia, hypomagnesemia, sindrom QT dawa kongenital, panggunaan obat-obatan sing dikenal kanggo ndawakake interval QT, terapi anthracycline dosis dhuwur kumulatif). Hipokalemia utawa hypomagnesemia sing bener sadurunge administrasi dasatinib.
Pulmonary Arterial Hypertension (PAH)
Muga-muga nambah risiko pangembangan PAH. Bisa kedadeyan kapan wae sawise wiwitan terapi (umpamane, 8-60 wulan); kacarita paling asring ing patients karo comorbidities utawa nampa obatan liyane concomitantly. Bisa dibalèkaké nalika mungkasi dasatinib.
Evaluasi pasien kanggo manifestasi penyakit kardiopulmoner sadurunge lan sajrone terapi dasatinib. Coba PAH ing sembarang pasien kanthi dyspnea, lemes, hipoksia, lan retensi cairan; Nanging, ora kalebu etiologi liyane dyspnea sadurunge miwiti prosedur diagnostik invasif kanggo PAH.
Interupsi terapi sing diiringi pemantauan kanggo perbaikan bisa dianggep yen PAH dicurigai. Yen PAH dikOnfirmasi (contone, kanthi kateterisasi jantung), mandhegake obat kasebut kanthi permanen.
Reaksi Dermatologis sing abot
Bisa nyebabake reaksi dermatologis sing abot, kalebu sindrom Stevens-Johnson lan erythema multiforme.
Nyetop kanthi permanen ing pasien sing ngalami reaksi dermatologis sing abot sajrone perawatan lan ora ana etiologi liyane. kanggo reaksi bisa dingerteni.
Sindrom Lysis Tumor
Bisa nambah risiko sindrom lisis tumor, umume ing pasien sing tahan penyakit imatinib ing fase lanjut.
Amarga potensial sindrom lisis tumor, njaga hidrasi sing cukup, tingkat asam urat sing bener sadurunge miwiti terapi karo dasatinib, lan ngawasi tingkat elektrolit sajrone terapi. Pasien karo penyakit fase lanjut lan/utawa beban tumor sing dhuwur bisa uga duwe risiko tambah sindrom lisis tumor lan kudu dipantau luwih kerep.
Morbiditas lan Mortalitas Janin/Neonatal
Bisa nyebabake cilaka janin; keracunan embriofetal lan teratogenicity wis kacarita ing manungsa. Aja meteng sajrone terapi. Yen digunakake nalika meteng utawa yen pasien meteng, kabar babagan bebaya janin sing potensial.
Wong wadon potensial reproduksi lan lanang karo pasangan wadon kasebut kudu nggunakake kontrasepsi sing efektif sajrone terapi lan 30 dina sawise dosis pungkasan.
Wong wadon sing lagi mbobot ora kena nangani tablet dasatinib sing remuk utawa pecah.
Efek kanggo Wutah lan Pangembangan Pasien Anak
Bisa mengaruhi wutah lan perkembangan balung ing pasien bocah.
Ngawasi wutah lan perkembangan balung sajrone terapi ing pasien bocah.
Hepatotoksisitas
Hepatotoksisitas kanthi paningkatan bilirubin, AST, ALT, lan fosfatase alkalin kacarita. Ngawasi transaminase ing awal lan saben wulan utawa minangka indikasi klinis sajrone terapi. Ngurangi utawa nyegah dosis dasatinib utawa mungkasi terapi kanthi permanen adhedhasar keruwetan hepatotoksisitas. Nalika ditindakake kanthi kemoterapi, paningkatan transaminase lan hiperbilirubinemia dilaporake. Ngawasi fungsi ati nalika dasatinib digunakake ing kombinasi karo kemoterapi.
Pasien sing ora toleran laktosa
Dosis saben dina 140 mg ngemot 189 mg laktosa monohidrat; Dosis saben dina 100 mg ngemot 135 mg laktosa monohidrat.
Populasi Tertentu
KandhutanBisa nyebabake cilaka janin.
LaktasiOra dingerteni manawa dasatinib disebar ing susu manungsa. Mungkasi nyusoni amarga ana risiko potensial kanggo nyusoni bayi.
Panggunaan PediatrikNgawasi wutah lan perkembangan balung ing pasien pediatrik.
Keamanan lan khasiat ora ditetepake ing pasien <18 taun sing wis diobati sadurunge Ph+ accelerated utawa myeloid utawa lymphoid blast phase CML.
Keamanan lan khasiat monoterapi dasatinib dievaluasi ing pasien pediatrik ≥1 taun karo CML fase kronis sing anyar didiagnosis. Keamanan lan khasiat uga wis dituduhake ing pasien pediatrik ≥1 taun kanthi Ph + ALL sing mentas didiagnosis. Ora ana data ing pasien pediatrik <1 taun.
Efek sing ora becik tumrap pertumbuhan lan perkembangan balung lan osteopenia kelas 1 sing dilapurake ing pasien pediatrik. Sakabèhé, profil safety ing pasien pediatrik bisa dibandhingake karo sing dilapurake ing pasien diwasa.
Paparan sistemik saka dasatinib sawise administrasi tablet dasatinib sing disebar ing jus ana 36% luwih murah tinimbang tablet utuh ing 5 pasien 2-10 taun. umur karo Ph + ALL. Khasiat lan safety saka nyebarake tablet dasatinib durung ditetepake.
Panggunaan GeriatrikOra ana bedane khasiat sing signifikan dibandhingake karo wong diwasa sing luwih enom, nanging pasien sing umure ≥65 taun luwih cenderung ngalami keracunan.
Gangguan HepatikOra diteliti ing pasien kanthi gangguan hepatik (ALT lan/utawa AST>2,5 kali ULN lan/utawa total bilirubin>2 kali ULN); Nanging obat kasebut dimetabolisme sacara ekstensif ing ati.
Gagal GinjalGangguan ginjel ora SAMesthine bakal ngurangi reresik dasatinib.
Reresik kreatinin 21,6 mL/menit ora ana pengaruh klinis sing relevan marang farmakokinetik dasatinib.
Efek Samsaya Awon
Efek salabetipun kacarita ing 15% utawa luwih pasien sing nampa dasatinib minangka monoterapi myelosuppression, retensi cairan, diare, sirah, ruam, pendarahan, dyspnea, lemes, mual, lan muskuloskeletal nyeri.
Efek salabetipun kacarita ing 30% utawa luwih pasien pediatrik sing nampa dasatinib kanthi kombinasi karo kemoterapi kalebu mucositis, neutropenia febrile, pyrexia, diare, mual, muntah, nyeri muskuloskeletal, nyeri abdomen, batuk, sirah, ruam, lemes, konstipasi, aritmia, hipertensi, edema, infeksi, hipotensi, napsu suda, hipersensitivitas, dyspnea, epistaksis, neuropati perifer, lan owah-owahan kesadaran.
Apa obatan liyane bakal mengaruhi Dasatinib (Systemic)
Metabolisme utamane dening CYP3A4; inhibitor lemah CYP3A4.
Ora nyandhet isoenzim CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, utawa 2E1; ora nyebabake isoenzim CYP manungsa.
Obat-obatan sing Ngaruhi Enzim Mikrosomal Hepatik
Inhibitor CYP3A4: Potensi interaksi farmakokinetik (tambah konsentrasi plasma dasatinib). Coba obat alternatif sing ora ana utawa kurang potensial inhibisi enzim. Yen panggunaan bebarengan karo inhibitor CYP3A4 sing kuat ora bisa dihindari, coba ngurangi dosis dasatinib dadi 20 mg saben dina (yen dosis saiki 70 utawa 100 mg saben dina) utawa nganti 40 mg saben dina (yen dosis saiki 140 mg saben dina) adhedhasar pertimbangan farmakokinetik ( ora ana data klinis kanthi pangaturan dosis kasebut). Coba mungkasi dasatinib 40 utawa 60 mg yen inhibitor CYP3A4 perlu. Yen dasatinib ora ditrima sawise nyuda dosis, mandhegake inhibitor CYP3A4 utawa ngganggu terapi dasatinib nganti perawatan karo inhibitor CYP3A4 rampung. Sawise mandheg saka inhibitor CYP3A4 sing kuat, udakara udakara udakara 1 minggu sadurunge nambah dosis dasatinib.
Inducer CYP3A4: Interaksi farmakokinetik potensial (mudhun konsentrasi dasatinib plasma). Aja nggunakake concomitant saka kuat CYP3A4 inducer; nimbang obat alternatif kanthi potensial induksi enzim ora utawa kurang. Yen terapi bebarengan ora bisa dihindari, nimbang nambah dosis dasatinib lan ngawasi kanthi teliti pasien kanggo keracunan.
Obat sing Ngaruhi koagulasi
Potensi getihen; nggunakake antikoagulan lan obat-obatan sing nyandhet fungsi trombosit bebarengan kanthi ati-ati.
Obat Metabolisme dening Enzim Mikrosomal Hepatik
Substrat CYP3A4: Potensi interaksi farmakokinetik (konsentrasi substrat plasma tambah).
Obat lan Panganan Spesifik
Obat utawa Pangan
Interaksi
Komentar
Antacid (contone, kalsium karbonat) , aluminium lan magnesium hidroksida)
Konsentrasi dasatinib plasma bisa mudhun, sekunder amarga ketergantungan pH sing jelas saka kelarutan dasatinib. antasida ≥2 jam sadurunge utawa ≥2 jam sawise dosis dasatinib
Anticoagulants (contone, warfarin)
Bisa tambah risiko pendarahan
Gunakake bebarengan kanthi ati-ati
Anti jamur, azoles (yaiku, itrakonazol, ketokonazol, vorikonazol)
Konsentrasi plasma dasatinib bisa tambah lan tambah paparan dasatinib Ketoconazole: Tambah AUC dasatinib kaping lima lan konsentrasi puncak kaping papat
p>Aja nggunakake bebarengan yen bisa; yen terapi bebarengan perlu, ngawasi kanthi teliti kanggo keracunan lan nimbang ngurangi dosis dasatinib
Jus jeruk bali
Konsentrasi dasatinib plasma sing bisa meningkat
Aja nggunakake bebarengan
Antagonis reseptor histamin H2 (contone, cimetidine, famotidine, ranitidine)
Konsentrasi dasatinib plasma bisa mudhun, sekunder amarga ketergantungan pH sing jelas saka kelarutan dasatinib Famotidine : Ngurangi AUC dasatinib lan konsentrasi puncak nganti 61-63% nalika diwenehi 10 jam sadurunge dasatinib
Panganggo bareng ora dianjurake
Inhibitor pompa proton (e.g., esOmeprazole, lansoprazole, omeprazole, Pantoprazole , rabeprazole)
Konsentrasi dasatinib plasma bisa mudhun, sekunder amarga gumantung pH sing jelas saka kelarutan dasatinib Omeprazole: AUC dasatinib lan konsentrasi puncak mudhun nganti 42-43% nalika diwenehi 22 jam sadurunge dasatinib
Ora disaranake nggunakake bebarengan
Rifamycins (rifabutin, rifampin)
Konsentrasi plasma dasatinib plasma lan AUC saka dasatinib Rifampin bisa mudhun: AUC dasatinib lan konsentrasi puncak mudhun nganti 81-82%
Aja nggunakake bebarengan yen bisa; yen terapi bebarengan perlu, tambahake dosis dasatinib lan ngawasi kanthi teliti kanggo keracunan
St. John's wort (Hypericum perforatum)
Potensi penurunan konsentrasi dasatinib plasma sing ora bisa diprediksi
Panganggo bareng ora dianjurake
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