Fluorouracil (Systemic)
Jeneng merek: Adrucil
Kelas obat:
Agen Antineoplastik
Panganggone Fluorouracil (Systemic)
Kanker
Pengobatan adenokarsinoma usus besar, rektum, payudara, lambung, lan pankreas.
Tambahan operasi kanggo perawatan macem-macem tumor padhet (contone, adenokarsinoma saka kolon, karsinoma rektum).
Kanker Kolorektal
Obat pilihan (digabungake karo leucovorin utawa levoleucovorin lan obat liyane [contone, irinotecan, oxaliplatin]) kanggo kanker kolorektal lanjut ing setelan adjuvant utawa metastatik.
Rejimen ganda (yaiku, fluorouracil, oxaliplatin, lan leucovorin utawa levoleucovorin [FOLFOX]; fluorouracil, irinotecan, lan leucovorin utawa levoleucovorin [FOLFIRI]; Capecitabine lan oxaliplatin [CapeOx] standar); perawatan kanggo adjuvant utawa perawatan paliatif kanker kolorektal lanjut.
Fluorouracil digabungake karo leucovorin utawa levoleucovorin minangka pilihan perawatan sing bisa ditampa ing setelan sumber daya winates utawa ing pasien sing ora bisa ngidinke regimen doublet.
Jadwal mingguan fluorouracil/leucovorin (dosis dhuwur) leucovorin utawa regimen Roswell Park) nduweni khasiat sing padha karo jadwal saben wulan (dosis kurang utawa jadwal Mayo Clinic), nanging jadwal mingguan minangka regimen sing disenengi kanggo terapi adjuvant amarga gampang digunakake lan kurang keracunan. (Deleng Kanker Kolorektal ing Dosis lan Administrasi.)
Dua wulan, jadwal infus IV terus-terusan fluorouracil/leucovorin (regimen LV5FU2 utawa deGramont) uga dievaluasi minangka terapi adjuvant lan ditampilake luwih aman tinimbang regimen injeksi IV langsung saka obat kasebut. obat-obatan. Versi sing disederhanakake saka regimen iki uga dievaluasi. (Deleng Kanker Kolorektal ing Dosis lan Administrasi.)
Peran terapi adjuvant regional (contone, vena portal utawa infus arteri hepatik† [off-label]) kanggo metastase ati mbutuhake elucidation luwih.
Leucovorin lan levoleucovorin nambah sitotoksisitas, potentiate aktivitas antineoplastik fluorouracil, lan nambah respon kanggo perawatan karsinoma kolorektal lanjut.
Leucovorin lan levoleucovorin bisa nambah risiko keracunan GI fluorouracil (contone, diare, mual, stomatitis, muntah) lan myelosuppression.
Kanker Payudara
Digabungake karo obat liya (contone, siklofosfamid, doxorubicin, methotrexate) minangka tambahan kanggo operasi lan kanggo kanker payudara metastatik.
Putusan babagan nggunakake terapi endokrin adjuvan kanthi utawa tanpa kemoterapi kombinasi sekuensial bisa dipandu dening alat prognostik, kayata skor kambuh adhedhasar asil tes 21-gen, kanggo prédhiksi keuntungan mutlak saka kombinasi kemoterapi saliyane adjuvant. terapi endokrin.
Tambahan operasi, bisa nambah asil.
Kanker Esophagus
Wis digunakake piyambak lan ing terapi kombinasi (contone, karo cisplatin) kanggo perawatan kanker esophageal lokal utawa lanjut† [off-label].
Kanker Sirah lan Gulu
Wis digunakake ing kombinasi kemoterapi kanggo karsinoma sel skuamosa metastatik utawa ambalan saka sirah lan gulu† [off-label].
Wis digunakake ing kombinasi kemoterapi karo terapi radiasi kanggo perawatan paliatif kanker sirah lan gulu sing ora bisa diobati sacara lokal, lan kanggo pengawetan laring ing kanker laring utawa hypopharyngeal sing maju sacara lokal.
Digunakake kanthi kombinasi karo docetaxel lan cisplatin minangka terapi induksi sadurunge radioterapi utawa kemoradioterapi ing perawatan karsinoma sel skuamosa lokal maju ing sirah lan gulu.
Kanker Serviks
Wis digunakake ing kombinasi karo cisplatin bebarengan karo terapi radiasi kanggo kanker serviks invasif† [off-label].
Kanker serviks metastatik utawa kambuh† [off-label].
Karsinoma Sel Ginjal
Wis digunakake piyambak utawa ing regimen kombinasi kanggo perawatan karsinoma sel ginjel metastatik†.
Tumor Carcinoid
Wis digunakake kanggo perawatan tumor carcinoid†.
Panganggone Liyane
Wis digunakake minangka terapi lini kedua ing perawatan kanker epitel ovarium†, kalebu penyakit refraktori platinum. Uga, kanker ati† (contone, hepatoblastoma†).
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Carane nggunakake Fluorouracil (Systemic)
Administrasi
Administrasi IV.
Wis diwenehake kanthi infus regional menyang suplai getih vena utawa arteri saka tumor† (contone, vena portal utawa infus arteri hepatik kanggo metastase ati).
Administrasi IV
Kanggo informasi kompatibilitas solusi lan obat, deleng Kompatibilitas ing Stabilitas.
Paket massal apotek 2,5 utawa 5-g ditujokake kanggo persiapan dosis individu , ora kanggo infus IV langsung.
Gunakake jalur IV sing wis ditemtokake kanggo ngatur fluorouracil kanthi injeksi IV langsung.
Kanggo rejimen infus IV, gunakake fluorouracil liwat kateter vena sentral nggunakake infus sing dikontrol. piranti (contone, pompa).
Aja ekstravasasi.
PengenceranOra ana pengenceran sing dibutuhake kanggo formulasi injeksi biasa.
Tingkat AdministrasiAdministrasi kanthi injeksi IV langsung utawa terus-terusan Infus IV.
Dosis
Dosis adhedhasar bobot nyata.
Bisa ngetung dosis adhedhasar area lumahing awak.
Jadwal dosis lan dosis individu adhedhasar jinis tumor, regimen spesifik, respon klinis, lan komorbiditas sing padha. agen kemoterapi.
Wong diwasa
Kanker kolorektalManeka warna rejimen dosis kombinasi fluorouracil/leucovorin wis digunakake.
IVInjeksi IV langsung: 500 mg/m2 kanthi injeksi IV langsung kanthi kombinasi karo leucovorin utawa levoleucovorin ing dina 1, 8, 15, 22, 29, lan 36 ing saben siklus 8 minggu.
Infus IV: 400 mg/m2 kanthi injeksi IV langsung ing dina 1 banjur 2400-3000 mg/m2 minangka infus IV terus-terusan sajrone 46 jam saben 14 dina kanthi kombinasi karo leucovorin utawa levoleucovorin kanthi utawa tanpa oxaliplatin utawa irinotecan.
Regimen Kombinasi: Fluorouracil, Leucovorin, lan Oxaliplatin (FOLFOX) IVDina 1: Oxaliplatin 85 mg/m2 lan leucovorin 200 mg/m2 bebarengan (ing wadhah kapisah nggunakake set administrasi tipe Y) kanthi infus IV luwih saka 2 jam, banjur fluorouracil 400 mg / m2 kanthi injeksi IV langsung, banjur fluorouracil 600 mg / m2 kanthi infus IV sajrone 22 jam.
Dina 2: Leucovorin 200 mg/m2 kanthi infus IV sajrone 2 jam, banjur fluorouracil 400 mg/m2 kanthi injeksi IV langsung, banjur fluorouracil 600 mg/m2 kanthi infus IV sajrone 22 jam.
Jadwal ing ngisor iki uga digunakake: Oxaliplatin 85–100 mg/m2 lan leucovorin 400 mg/m2 kanthi infus IV sajrone 2 jam, banjur fluorouracil 400 mg/m2 kanthi injeksi IV langsung, banjur fluorouracil 2400-3000 mg/m2 kanthi infus IV sajrone 46 jam.
Baleni siklus saben 2 minggu.
Regimen Kombinasi: Fluorouracil, Leucovorin, lan Irinotecan (FOLFIRI) IVIrinotecan 180 mg/m2 lan leucovorin 400 mg/m2 diwènèhaké bebarengan kanthi infus IV sajrone 2 jam, banjur fluorourasil 400 mg/m2 kanthi injeksi IV langsung, banjur fluorourasil 2400-3000 mg/m2 kanthi infus IV sajrone 46 jam. ; siklus baleni saben 2 minggu.
Regimen Kombinasi: Fluorouracil, Leucovorin, Oxaliplatin, lan Irinotecan (FOLFOXIRI) IVIrinotecan 165 mg/m2 kanthi infus IV sajrone 1 jam, banjur leucovorin 200 mg/m2 lan oxaliplatin 85 mg/m2 kanthi administrasi bebarengan. infus IV liwat 2 jam, lan banjur fluorouracil 3200 mg / m2 dening infus IV liwat 48 jam; siklus baleni saben 2 minggu.
Jadwal Bulanan (Rejimen Klinik Mayo) Injeksi Langsung IVLeucovorin 20 mg/m2 IV utawa levoleucovorin 10 mg/m2 IV disusul fluorouracil 425 mg/m2 IV; ngatur fluorouracil lan salah siji leucovorin utawa levoleucovorin saben dina kanggo 5 dina berturut-turut lan mbaleni regimen ing interval 4 minggu kanggo 2 kursus tambahan; sesampunipun, bisa mbaleni regimen ing interval saka 4-5 minggu kasedhiya keracunan saka Course sadurungé wis mantun rampung. Asring diterbitake kanggo total 6 siklus ing setelan adjuvant.
Utawa, leucovorin 200 mg/m2 IV utawa levoleucovorin 100 mg/m2 IV liwat ≥3 menit banjur fluorouracil 370 mg/m2 IV; ngatur fluorouracil lan salah siji leucovorin utawa levoleucovorin saben dina kanggo 5 dina berturut-turut lan mbaleni regimen ing interval 4 minggu kanggo 2 kursus tambahan; sesampunipun, bisa mbaleni regimen ing interval saka 4-5 minggu kasedhiya keracunan saka Course sadurungé wis mantun rampung.
Setel dosis fluorouracil ing kursus sabanjure miturut toleransi; nyuda dosis fluorouracil saben dina kanthi 20% kanggo keracunan hematologis utawa GI sing moderat ing kursus sadurunge lan nganti 30% kanggo keracunan abot (dosis leucovorin utawa levoleucovorin ora diatur).
Bisa nambah dosis fluorouracil nganti 10% yen ora ana keracunan. kedadeyan ing kursus sadurunge.
Jadwal Mingguan (Rejimen Roswell Park) IV InfusLeucovorin 500 mg/m2 minangka infus IV 2 jam banjur fluorouracil 500 mg/m2 minangka injeksi IV alon sing diwenehake 1 jam sawise wiwitan infus leucovorin. . Atur loro obat saben minggu kanggo 6 minggu berturut-turut banjur istirahat 2 minggu; siklus baleni saben 8 minggu kanggo total 4 kursus ing setelan adjuvant.
Setel dosis fluorouracil ing kursus sabanjure miturut toleransi; nyuda dosis fluorouracil saben dina kanthi 20% kanggo hematologis moderat utawa keracunan GI ing kursus sadurunge lan nganti 30% kanggo keracunan abot (dosis leucovorin ora diatur).
Bisa nambah dosis fluorouracil nganti 10% yen ora ana keracunan ing kursus sadurunge.
Jadwal Dwimonthly (Modified deGramont Regimen) IV InfusLeucovorin 400 mg/m2 minangka infus IV 2-jam ing dina 1 ngiring dening fluorouracil 400 mg/m2 minangka injeksi IV ing dina 1; banjur fluorouracil 1500 mg / m2 minangka infus IV terus-terusan sajrone 23 jam ing dina 1 lan 2 (yaiku, total 3000 mg / m2 kanthi infus IV terus-terusan sajrone 46 jam); baleni siklus saben 2 minggu.
Kanker PayudaraManeka warna rejimen kombinasi wis digunakake; takon protokol sing diterbitake kanggo dosis lan cara lan urutan administrasi.
Ngindhari pangurangan dosis sewenang-wenang saka kemoterapi kombinasi adjuvant; intensitas dosis katon minangka faktor penting sing mengaruhi asil klinis ing awal kanker payudara node-positif (nambah respon kanthi intensitas tambah).
IV500 utawa 600 mg/m2 IV ing dina 1 lan 8 saben siklus 28 dina kanthi total 6 siklus kanthi kombinasi karo regimen berbasis siklofosfamid.
Regimen Kombinasi: Cyclophosphamide, Methotrexate, lan Fluorouracil IVRejimen sing ngemot fluorouracil IV kanthi kombinasi karo siklofosfamid oral lan methotrexate IV diterangake ing tabel.
Obat
Dosis
Dina Administrasi saben Siklus
Fluorouracil
600 mg/m2 IV (≤60 taun)
Dina 1 lan 8
Siklofosfamid
100 mg/m2 oral
Hari 1 nganti 14
Methotrexate
40 mg/m2 IV (≤60 taun)
Dina 1 lan 8
Baleni saben wulan (yaiku, ngidini wektu istirahat 2 minggu ing antarane siklus).
Total 6-12 siklus (yaiku, terapi 6-12 sasi); superioritas klinis antarane regimen 6- versus 12 sasi ora dituduhake.
Dosis awal fluorouracil lan methotrexate wis dikurangi ing pasien> 60 taun. (Deleng Pasien Geriatrik ing Populasi Khusus.)
Uga, dosis dikurangi yen myelosuppression berkembang.
Regimen Sekuensial: Cyclophosphamide, Methotrexate, lan Fluorouracil Plus DoxorubicinIng awal kanker payudara lan> 3 kelenjar getah bening aksila positif, tambahan doxorubicin bisa nambah asil, lan regimen urutan (yaiku, sawetara kursus doxorubicin pisanan) bisa luwih efektif tinimbang rejimen gantian; ora entuk manfaat tambahan nalika kurang node positif.
IVKaping pisanan, doxorubicin hydrochloride 75 mg/m2 IV kanthi interval 3 minggu kanggo 4 dosis.
Sabanjure, fluorouracil 600 mg/m2 IV, metotreksat 40 mg/m2 IV, lan siklofosfamid 600 mg/m2 IV kanthi interval 3 minggu kanggo 8 siklus.
Total babagan terapi 9 sasi.
Umume, myelosuppression wis tundha siklus tinimbang ngurangi dosis.
Kanker lambung IV200–1000 mg/m2 minangka infus IV terus-terusan sajrone 24 jam kanthi kombinasi karo regimen basis platinum. Hubungi protokol sing diterbitake kanggo frekuensi dosis lan durasi saben siklus kanggo regimen spesifik.
Kanker Pankreas IV400 mg/m2 kanthi injeksi IV langsung ing dina 1 banjur 2400 mg/m2 minangka infus IV terus-terusan liwat 46 jam saben 14 dina ing kombinasi karo leucovorin utawa minangka bagéan saka regimen multi-obat sing ngandhut leucovorin.
Modifikasi Dosis kanggo ToksisitasKanggo diare utawa mucositis grade 3 utawa 4, myelosuppression grade 4, utawa grade 2 utawa 3 erythrodysesthesia palmar-plantar (sindrom tangan-kaki), terapi nahan; Diterusake terapi kanthi dosis suda nalika keracunan wis rampung utawa mundhak dadi kelas 1.
Tunda terapi sementara yen kardiotoksisitas (yaiku, angina, infark miokard utawa iskemia, aritmia, gagal jantung) berkembang ing pasien tanpa riwayat saka penyakit arteri koroner utawa disfungsi jantung; uga nahan terapi yen encephalopathy hyperammonemic utawa efek neurologis (yaiku, sindrom cerebellar akut, kebingungan, disorientasi, ataxia, gangguan visual) kedadeyan. Produsen ora menehi rekomendasi dosis kanggo nerusake terapi fluorouracil sawise pangembangan kardiotoksik, encephalopathy hiperamonemik, utawa efek neurologis.
Populasi Khusus
Pasien Geriatri
Kanker PayudaraIng pasien> 60 taun sing nampa siklofosfamid oral, methotrexate IV, lan terapi kombinasi fluorourasil IV, ngurangi dosis awal metotreksat dadi 30 mg/m2 lan dosis fluorourasil dadi 400 mg/m2.
Pènget
Kontraindikasi
Pènget / PancegahanKekurangan Aktivitas Dipyrimidine Dehydrogenase (DPD)
Awitan awal akut utawa keracunan sing luar biasa abot bisa uga nuduhake ora ana aktivitas DPD sing meh lengkap utawa total; nyegah utawa mungkasi fluorouracil kanthi permanen ing pasien kasebut.
Mutasi heterozigot homozigot utawa senyawa tartamtu ing gen DPD nyebabake ora ana aktivitas DPD lengkap utawa meh lengkap. Patients karo mutasi kuwi ana ing tambah risiko kanggo akut awal-awal lan abot, ngancam nyawa, utawa keracunan fatal (contone, mucositis, diare, neutropenia, neurotoxicity). Pasien kanthi aktivitas DPD parsial uga bisa nambah risiko keracunan sing abot, ngancam nyawa, utawa fatal.
Kaamanan ora ditetepake ing pasien sing ora ana aktivitas DPD.
Data ora cukup kanggo ndhukung rekomendasi dosis kanggo sing duwe aktivitas DPD parsial.
Efek Jantung
Iskemia/infark miokard, gagal jantung, aritmia, lan angina (kalebu angina varian Prinzmetal).
Administrasi obat kanthi infus IV terus-terusan lan anané koroner. penyakit arteri bisa nambah risiko kardiotoksisitas.
Keamanan kanggo nerusake fluorouracil sawise resolusi kardiotoksik durung ditetepake.
Efek Sistem Saraf
Disorientasi, kebingungan, ataxia, gangguan visual, lan sindrom cerebellar akut kacarita. Data sing ora cukup babagan risiko nerusake fluorouracil sawise ngrampungake efek samping neurologis.
Ensefalopati hipermonemik, yen ora ana penyakit ati utawa sabab liyane sing bisa dingerteni, dilaporake. Status mental sing diowahi, kebingungan, disorientasi, ataxia, utawa koma ing ngarsane konsentrasi amonia serum sing luwih dhuwur, bisa kedadeyan ≤72 jam sawise wiwitan infus fluorouracil.
Yen encephalopathy hyperammonemic utawa efek neurologis kedadeyan, terapi sementara interupsi.
Toksisitas GI
Mucositis, stomatitis, lan esophagopharyngitis lan sloughing utawa ulcerasi mukosa sakteruse dilaporake luwih kerep sawise administrasi obat kanthi injeksi IV langsung dibandhingake karo administrasi infus IV terus. Diare kerep kedadeyan lan bisa uga abot.
Tunda sementara fluorouracil yen diare utawa mucositis kelas 3 utawa 4; nerusake tamba ing dosis suda nalika keracunan mutusaké utawa mbenakake kanggo grade 1. Potensi diare kanggo nimbulaké karusakan Clinical cepet lan pati ing patients nampa suda folates (leucovorin, levoleucovorin) concomitantly; ngawasi cedhak dibutuhake.
Miwiti penggantian cairan lan elektrolit utawa terapi antidiare yen perlu sacara klinis.
Sindrom tangan kaki
Palmar-plantar erythrodysesthesia (sindrom tangan-kaki) kacarita.
Rash eritematous, desquamative sing nyangkut tangan lan sikil, bisa uga diiringi sensasi tingling, nyeri, bengkak, lan eritema kanthi tenderness.
Yen sindrom sikil tangan kelas 2 utawa 3 kedadean, terapi interupsi sementara nganti keracunan wis rampung utawa mundhak dadi kelas 1.
Bisa diobati nganggo terapi piridoksin oral utawa emolien topikal (contone, krim tangan, balm udder).
Toksisitas Hematologis
Myelosuppression (contone, neutropenia, trombositopenia, anemia), kadhangkala abot utawa fatal, dilaporake. Jumlah neutrofil nadir biasane kedadeyan 9-14 dina sawise wiwitan terapi.
Entuk jumlah sel getih lengkap (CBC) sadurunge saben siklus perawatan, saben minggu (yen diwenehake saben minggu utawa jadwal sing padha), lan minangka klinis. dituduhake.
Yen myelosuppression kelas 4 dumadi, interupsi sementara terapi nganti keracunane ilang utawa mundhak dadi kelas 1.
Morbiditas lan Mortalitas Janin/Neonatal
Bisa njalari cilaka janin.
Anjurake wanita sing duwe anak lan wong lanang sing duwe pasangan wadon supaya nggunakake metode kontrasepsi sing efektif sajrone terapi fluorouracil lan munggah. nganti 3 sasi sawise dosis pungkasan saka obat kasebut.
Yen digunakake nalika meteng utawa yen pasien ngandhut, kabar yen ana bebaya kanggo janin.
Gangguan Kesuburan
Asil panaliten kewan nuduhake yen fluorouracil bisa ngrusak kesuburan lanang lan wadon.
Populasi Spesifik
KandhutanKategori D. (Deleng Morbiditas lan Mortalitas Janin/Neonatal miturut Ati-ati.)
LaktasiOra dingerteni manawa fluorouracil utawa metabolite disebarake menyang susu manungsa. Mungkasi nyusoni utawa obat kasebut.
Panggunaan PediatrikKeamanan lan khasiat ing bocah-bocah durung ditetepake.
Efek Sabar sing Umum
Stomatitis, esophagopharyngitis, anoreksia, mual, muntah, diare, leukopenia (utamane granulositopenia), trombositopenia, anemia, alopecia, dermatitis (utamane ruam makulopapular pruritic). >
Apa obatan liyane bakal mengaruhi Fluorouracil (Systemic)
Obat sing dimetabolisme dening Enzim Mikrosomal Hepatik
Substrat CYP2C9: Fluorouracil utawa metabolite bisa nyandhet CYP isoenzyme 2C9.
Obat Spesifik
Obat
Interaksi
Komentar
Antikoagulan kumarin (contone, warfarin)
Peningkatan sing signifikan sacara klinis ing parameter koagulasi (contone, wektu protrombin sing tambah [PT], tambah INR)
Ngawasi INR kanthi rapet utawa PT; nyetel dosis antikoagulan yen perlu
Leucovorin
Leucovorin potentiates sitotoksisitas fluorouracil ing kanker GI tartamtu
Leucovorin nambah keracunan fluorouracil
Digunakake kanggo keuntungan terapeutik ing kanker GI
Gunakake bebarengan kanthi ati-ati banget ing pasien geriatrik utawa debilitated; luwih cenderung ngalami keracunan serius
Levoleucovorin
Levoleucovorin nambah efek terapeutik fluorouracil ing kanker kolorektal
Levoleucovorin nambah keracunan fluorouracil
Digunakake kanggo kauntungan terapeutik ing kanker kolorektal
Gunakake bebarengan kanthi ati-ati banget ing pasien geriatrik utawa debilitated; luwih cenderung ngalami keracunan serius
Disclaimer
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