Carmustine
Kelas obat: Agen Antineoplastik
Panganggone Carmustine
Tumor Otak: Kemoterapi Konvensional
Tambahan terapi radiasi sawise operasi kanggo perawatan paliatif glioma ganas (yaiku, astrocytoma, ependymoma, medulloblastoma, glioma batang otak) lan tumor otak metastatik.
Ing antarane sawetara regimen kemoterapi sing disenengi kanggo astrocytoma anaplastik lan glioblastoma multiforme. Durung ditampilake kanggo nambah wektu kaslametané, nanging tren menyang tingkat kaslametané long-term sing luwih dhuwur (contone, ing 18 sasi) wis diamati.
Adjuvant utawa salvage therapy kanggo oligodendroglioma.
Pembedahan kanthi utawa tanpa terapi radiasi saiki dianggep minangka perawatan standar kanggo ependymoma lan medulloblastoma. Terapi radiasi dianggep minangka perawatan standar kanggo glioma batang otak.
Tumor Otak: Implan Wafer Intrakranial
Tambahan kanggo operasi lan radiasi kanggo perawatan glioma ganas tingkat dhuwur sing mentas didiagnosis. Antarane sawetara regimen kemoterapi sing disenengi kanggo astrocytoma anaplastik lan glioblastoma multiforme.
Tambahan kanggo operasi kanggo perawatan glioblastoma multiforme sing berulang.
Multiple Myeloma
Carmustine-containing regimens dianggep minangka terapi alternatif kanggo perawatan paliatif saka multiple myeloma.
Penyakit Hodgkin
Digunakake kanthi kombinasi karo agen liyane minangka terapi sekunder kanggo perawatan penyakit Hodgkin sing refrakter utawa kambuh.
Rejimen kombinasi sing ngemot agen liyane saiki luwih disenengi minangka terapi awal utawa alternatif. kanggo kanker iki.
Limfoma Non-Hodgkin
Digunakake ing kombinasi karo agen liyane minangka terapi sekunder kanggo perawatan limfoma non-Hodgkin sing refrakter utawa kambuh.
Rejimen kombinasi sing ngemot agen liyane saiki luwih disenengi minangka terapi awal utawa alternatif kanggo kanker kasebut.
Melanoma
Wis digunakake piyambak utawa ing terapi kombinasi kanggo perawatan paliatif melanoma metastatik† [off-label]; Nanging, tingkat respon kurang lan keracunan substansial mbatesi panggunaan carmustine iki.
Limfoma sel T kulit
Digunakake sacara topikal† [off-label] kanggo perawatan paliatif limfoma sel T kulit (mycosis fungoides)† [off-label].
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Carane nggunakake Carmustine
Umum
Administrasi
Administrasi kanthi infus IV utawa intracranial minangka implan wafer.
Wis diterbitake dening intra-arterial† [mati -label] (menyang arteri karotis) rute; Nanging, administrasi kasebut digandhengake karo keracunan okular (buta), encephalopathy fatal, lan kaslametané inferior.
Wis diterbitake topikal† [off-label] minangka solusi hidroalkohol 0,05-0,4% utawa minangka salep. , nanging formulir dosis kanggo panggunaan kasebut ora kasedhiya kanthi komersial ing AS; takon referensi khusus.
Administrasi IV
Kanggo informasi kompatibilitas solusi lan obat, deleng Kompatibilitas ing Stabilitas.
Botol mung kanggo panggunaan siji.
Gunakake wadhah kaca kanggo administrasi.
Ngalahake kanthi ati-ati (umpamane, gunakake sarung tangan); ngindhari paparan nalika nangani bubuk lan nyiyapake solusi IV.
Yen kena kulit utawa mukosa, enggal-enggal ngumbah area sing kena pengaruh kanthi sabun lan banyu.
RekonstitusiTambahake 3 ml pelarut sing diwenehake dening pabrikan (alkohol dehidrasi steril [absolut]) menyang vial sing ngemot 100 mg carmustine; banjur tambahake 27 ml banyu steril kanggo injeksi. Solusi sing diasilake ngandhut 3,3 mg/mL carmustine ing etanol 10%.
PengenceranDiencerke nganggo injeksi dekstrosa 5%.
Tingkat administrasiDiwenehake kanthi infus IV sajrone 1-2 jam. Administrasi luwih cepet sing ana gandhengane karo efek samping. (Deleng Efek Lokal ing Ati-ati.)
Implan Wafer Intracranial
Nangani kanthi ati-ati (bahan sitotoksik); gunakake sarung tangan bedah kaping pindho lan sarung tangan njaba dibuwang menyang wadhah sampah biohazard sawise digunakake.
Wafer sing pecah setengah bisa digunakake; dibuwang ing wadhah biohazard yen pecah dadi >2 lembar.
Kirimake kantong laminasi aluminium foil sing ngemot wafer menyang kamar operasi; aja mbukak nganti siap kanggo implan. Permukaan njaba kantong foil njaba ora steril.
Gunakake piranti bedah khusus kanggo nangani wafer carmustine kanggo implan wafer.
Implant intrakranial ing rongga reseksi sawise reseksi tumor otak bedah.
Lebokake selulosa regenerasi teroksidasi (Surgicel) ing ndhuwur wafer kanggo ngamanake permukaan rongga reseksi. Sawise diselehake wafer, irigasi rongga reseksi lan nutup dura kanthi cara kedap banyu kanggo nyuda resiko bocor CSF.
Dosis
Dewasa
Tumor Otak IVMinangka monoterapi ing pasien sing sadurunge ora diobati, 150-200 mg / m2 diwènèhaké minangka dosis siji utawa ing dosis dibagi (contone, 75-100 mg / m2 ing 2 dina berturut-turut) kanthi interval paling sethithik 6 minggu.
Ngurangi dosis yen digunakake ing kombinasi karo obat myelosuppressive liyane utawa ing pasien karo fungsi sumsum balung kompromi.
Setel dosis sakteruse adhedhasar jumlah getih nadir saka dosis sadurunge (pirsani Modifikasi Dosis kanggo Toksisitas miturut Dosis lan Administrasi).
Implan Wafer IntrakranialNganti 8 wafer (dosis total carmustine: 61,6 mg) intracranial kanggo nutupi rongga reseksi sabisa-bisa (diijini tumpang tindih tipis). Yen ukuran lan wangun rongga ora ngidini panggonan 8 wafer, gunakake jumlah maksimal.
Aja nyelehake >8 wafer sacara intracranial saben prosedur bedhah.
Ing uji klinis, kemoterapi ditindakake. ditahan paling sethithik 4 minggu (6 minggu kanggo nitrosoureas) sadurunge lan 2 minggu sawise operasi; Terapi radiasi sinar eksternal ditindakake ora luwih saka 3 minggu sawise operasi.
Multiple Myeloma IVMinangka monoterapi ing pasien sing sadurunge ora diobati, 150-200 mg / m2 diwenehake minangka dosis siji utawa ing dosis sing dibagi (umpamane, 75). –100 mg/m2 ing 2 dina berturut-turut) kanthi interval paling sethithik 6 minggu.
Turunake dosis yen digunakake ing kombinasi karo obat mielosupresif liyane utawa ing pasien kanthi fungsi sumsum balung sing rusak.
Nyetel dosis sakteruse adhedhasar jumlah getih nadir saka dosis sadurunge (pirsani Modifikasi Dosis kanggo Toksisitas miturut Dosis lan Administrasi).
Penyakit Hodgkin IVMinangka monoterapi ing pasien sing sadurunge ora diobati, 150-200 mg/m2 diwenehake minangka dosis siji utawa ing dosis dibagi (contone, 75-100 mg/m2 ing 2 dina berturut-turut) ing interval paling sethithik 6 minggu. fungsi sumsum balung.
Setel dosis sabanjure adhedhasar jumlah getih nadir saka dosis sadurunge (pirsani Modifikasi Dosis kanggo Toksisitas miturut Dosis lan Administrasi).
Limfoma IV Non-HodgkinMinangka monoterapi ing pasien sing sadurunge ora diobati, 150-200 mg/m2 diwènèhaké minangka dosis siji utawa ing dosis sing dibagi (contone, 75-100 mg/m2 ing 2 dina berturut-turut) kanthi interval paling sethithik 6 minggu.
Turunake dosis yen digunakake ing kombinasi karo obat myelosuppressive liyane utawa ing pasien kanthi fungsi sumsum balung sing kompromi.
Setel dosis sabanjure adhedhasar jumlah getih nadir saka dosis sadurunge (pirsani Modifikasi Dosis kanggo Toksisitas ing Dosis lan Administrasi).
Limfoma sel T kulit† TopikalDosis topikal biasanipun 10 mg sapisan saben dina kanggo 7-14 minggu (maksimal: 17 minggu). Yen respon ora cukup, sawise interval istirahat 6 minggu, administrasi terapi topikal kaping pindho kanthi 20 mg sapisan dina kanggo 4-8 minggu, kaya sing ditrima.
Formulir dosis topikal ora kasedhiya kanggo komersial ing AS; takon referensi khusus kanggo informasi khusus babagan panggunaan topikal.
Modifikasi Dosis kanggo Toksisitas
Kemoterapi KonvensionalAja ngulang kursus nganti jumlah leukosit>4000/mm3, jumlah trombosit>100.000/mm3, lan jumlah neutrofil sing cukup ana ing periferal. apusan getih.
Toksisitas sumsum balung iku kumulatif; nyetel dosis sakteruse adhedhasar jumlah getih nadir saka dosis sadurunge.
Tabel 1. Penyesuaian Dosis kanggo Toksisitas Hematologis Adhedhasar Nadir Sawise Dosis Sadurunge (rekomendasi pabrikan)Leukosit (sel/mm3)
Platelet (sel/mm3)
Persentase Dosis Sadurunge sing Diwenehi
>4000
>100.000
100%
3000–3999
75.000–99.999
100%
2000–2999
25.000–74.999
70%
<2000
<25,000
50%
Utawa, kanggo ngindhari overdosis potensial sing ana gandhengane karo modifikasi sing disaranake pabrikan, sawetara dokter nyaranake nyuda dosis sabanjure nganti 25% nalika nadir trombosit 50,000-74,999 / mm3; dening 50% kanggo nadir 25.000-49.999 / mm3; lan 75% kanggo nadir <25.000/mm3.
Batesan Resep
Dewasa
Tumor Otak Implan Wafer IntrakranialMaksimum 8 wafer saben prosedur bedhah.
Populasi Khusus
Pasien Geriatrik
Pilih dosis IV kanthi ati-ati amarga nyuda fungsi ati, ginjel, lan/utawa jantung lan penyakit bebarengan lan terapi obat sing gegandhengan karo umur. (Deleng Panggunaan Geriatrik ing Caution.)
Pènget
Kontraindikasi
Pènget / PancegahanPènget
Efek Hematologi
Risiko myelosuppression (contone, thrombocytopenia, leukopenia) sawise IV carmustine; efek telat lan kumulatif. (Deleng Warning Boxed.) Trombositopenia umume luwih abot tinimbang leukopenia, nanging loro-lorone dianggep racun sing bisa mbatesi dosis. Anemia dilapurake kurang kerep lan kurang abot.
Sakwise administrasi IV, trombositopenia lan leukopenia dumadi ing kira-kira 4 lan 5-6 minggu, lan tetep nganti 1-2 minggu.
Dosis bola-bali digandhengake karo myelosuppression sing luwih abot lan luwih dawa.
Gunakake kanthi ati-ati ing pasien kanthi jumlah platelet, leukosit, utawa eritrosit sing depresi.
Efek PulmonalKanthi IV carmustine, risiko dosis- gegandhengan, kadhangkala fatal, keracunan paru-paru (ditandani dening infiltrat paru-paru lan / utawa fibrosis). (Deleng Warning Boxed.) Faktor risiko kalebu terapi sing dawa (kanthi dosis kumulatif>1400 mg/m2) lan riwayat penyakit paru-paru.
Risiko fibrosis paru-paru sing telat (kedadeyan nganti 17 taun sawise perawatan sajrone perawatan. kanak-kanak lan awal remaja); bisa ngurangi fungsi paru-paru utawa mati. (Deleng Panganggone Pediatrik ing Ati-ati.)
Tindakake tes fungsi paru sadurunge wiwitan lan asring sajrone terapi. Patients with baseline forced vital capacity (FVC) or pulmonary diffusion capacity for carbon monoxide (DLCO) <70% saka prediksi nilai utamane beresiko.
Secondary MalignanciesRisiko ganas sekunder sawise nggunakake jangka panjang nitrosoureas .
Komplikasi Implan IntracranialEfek massa intracerebral ora responsif marang kortikosteroid sing dilapurake, kalebu siji kasus sing nyebabake herniasi otak. Edema otak kanthi efek massa (amarga tumor kambuh, infeksi intrakranial, utawa nekrosis) bisa uga mbutuhake operasi maneh lan, ing sawetara kasus, mbusak sisa wafer utawa wafer.
Risiko kejang; Wektu rata-rata kanggo wiwitan yaiku 3,5 dina.
Pembentukan kista amben tumor ora responsif marang kortikosteroid dosis dhuwur sing dilapurake; mbutuhake operasi maneh kanggo drainase sawise implantasi wafer carmustine.
Pantau pasien kanthi teliti kanggo kemungkinan komplikasi craniotomy (contone, kejang, infeksi intrakranial, penyembuhan tatu sing ora normal, edema otak).
Morbiditas janin/Neonatal lan MortalitasKamungkinan cilaka janin; teratogenicity lan embriotoxicity dituduhake ing kéwan. Aja meteng sajrone terapi. Yen digunakake nalika meteng utawa yen pasien meteng, kabar babagan bebaya janin.
Toksisitas Utama
Efek LokalInfus IV kanthi cepet bisa nyebabake siram kulit sing intensif lan suffusion saka konjungtiva; efek kasebut kedadeyan sajrone 2 jam lan tetep nganti 4 jam sawise administrasi IV. Uga digandhengake karo nyeri sing kuat lan kobong ing situs injeksi; trombosis arang banget.
Kanthi implan wafer intrakranial, dehiscence tatu; marasake awakmu tatu tundha; subdural, subgaleal, utawa efusi tatu; lan bocor CSF kacarita.
Komplikasi InfèksiusKanthi implan wafer intrakranial, abses, meningitis, lan radhang paru-paru kacarita. Sepsis dilapurake nanging hubungan sebab akibat ora ditetepake.
Efek GIKanthi IV carmustine, mual lan muntah sing ana gandhengane karo dosis dilaporake sajrone 2 jam lan tetep nganti 4-6 jam. Premedikasi kanthi antiemetik bisa nyuda utawa nyegah.
Efek HepatikSawise terapi IV, paningkatan transaminase serum, fosfatase alkalin, lan bilirubin sing bisa dibatalake dilaporake. Kemungkinan disfungsi hepatik. Ngawasi fungsi ati sacara periodik.
Efek GinjalSawise terapi IV sing dawa (kanthi dosis kumulatif gedhe), azotemia progresif, nyuda ukuran ginjel, lan gagal ginjel dilaporake. Kerusakan ginjel dilaporake sok-sok ing pasien sing nampa dosis total sing luwih murah. Monitor fungsi ginjel sacara periodik.
Pancegahan Umum
Terapi IVEvaluasi keuntungan carmustine nglawan risiko sing bisa ditindakake. Paling efek salabetipun bisa dibalèkaké yen dideteksi awal karo perawatan sing cocog (contone, nyuda dosis, mandheg, langkah-langkah koreksi sing cocog). Reinstitute kanthi ati-ati, nimbang risiko lan keuntungan.
Risiko hiperpigmentasi transien kulit kanthi paparan kulit sing ora disengaja; langsung ngumbah kulit utawa mukosa sing katon.
Implan Wafer IntracranialRisiko migrasi wafer saka rongga reseksi bedhah menyang sistem ventrikel, nyebabake hidrosefalus obstruktif. Yen komunikasi antarane rongga reseksi bedhah lan sistem ventrikel luwih gedhe tinimbang diameter wafer, tutup komunikasi kasebut sadurunge implantasi.
Peningkatan jaringan otak ing sekitar rongga reseksi (dituduhake kanthi CT scan utawa MRI) sawise implantasi intrakranial bisa uga nuduhake. edema lan inflamasi sing disebabake wafer utawa tumor.
Pemantauan TerapiKanthi terapi IV, monitor CBC saben minggu sajrone lan paling ora 6 minggu sawise saben dosis. Uga ngawasi tes fungsi paru, hepatik, lan ginjel kanthi periodik sajrone perawatan.
Populasi Spesifik
KandhutanKategori D. (Deleng Morbiditas lan Mortalitas Janin/Neonatal miturut Ati-ati.)
LaktasiOra dingerteni manawa carmustine disebarake menyang susu. Mungkasi nyusoni amarga ana risiko potensial kanggo nyusoni bayi. Ora dingerteni manawa konstituen polifeprosan 20 kopolimer (yaiku, carboxyphenoxypropane, asam sebacic) wafer intrakranial disebarake menyang susu.
Panggunaan PediatrikKeamanan lan khasiat IV carmustine ora ditetepake ing bocah-bocah. Fibrosis paru-paru fatal dilaporake kanthi wiwitan telat nganti 17 taun sawise perawatan IV tumor otak nalika bocah cilik utawa remaja. Resiko dhuwur banget kanggo keracunan paru-paru fatal, utamane ing bocah-bocah <5 taun nalika perawatan awal; kanthi ati-ati nimbang keuntungan lan risiko terapi ing pasien pediatrik.
Keamanan lan kesahihan implan wafer intrakranial ora ditetepake ing pasien pediatrik.
Panggunaan GeriatrikPengalaman sing ora cukup ing pasien ≥65 taun kanggo nemtokake manawa pasien geriatrik nanggapi beda karo wong diwasa sing luwih enom. Pilih dosis kanthi ati-ati amarga nyuda fungsi ati, ginjel, lan / utawa jantung sing gegandhengan karo umur lan potensial kanggo penyakit bebarengan lan terapi obat.
Carmustine sistemik diilangi sacara substansial dening ginjel; ngawasi fungsi ginjel sacara periodik amarga pasien geriatrik luwih cenderung ngalami penurunan fungsi ginjel.
Efek Samsaya Awon
Kanggo IV carmustine, infiltrat paru lan/utawa fibrosis, trombositopenia, leukopenia, anemia, mual, muntah, keracunan hepatik lan ginjel. (Deleng Pènget / Pancegahan ing Caution.)
Kanggo wafer intrakranial, hemiplegia, kejang, kebingungan, edema otak, sirah, asthenia, mual, muntah, konstipasi, infeksi, demam, afasia, penyembuhan abnormal, depresi, nyeri, ruam, ngantuk, gangguan wicara, tromboflebitis jero, alopecia.
Apa obatan liyane bakal mengaruhi Carmustine
Wafer Intrakranial
Ora ana studi interaksi obat resmi nganti saiki. Ing uji klinis, kemoterapi ditahan paling sethithik 4 minggu (6 minggu kanggo nitrosoureas) sadurunge lan 2 minggu sawise operasi. Implantasi magepokan karo radioterapi katon ora duwe keracunan jangka pendek utawa kronis; ing uji klinis, terapi radiasi sinar eksternal ditindakake >3 minggu sawise operasi.
Obat Spesifik
Obat
Interaksi
Komentar
Cimetidine
Potensiasi efek neutropenik lan trombositopenik saka carmustine
Mitomycin
Kamungkinan owah-owahan ing film luh, kanthi karusakan kornea lan konjungtiva. epitelium
Fenitoin
Konsentrasi fenitoin serum bisa mudhun
Pantau konsentrasi fenitoin serum kanthi ati-ati lan atur dosis sing cocog
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