Tezacaftor and Ivacaftor
Jeneng merek: Symdeko
Kelas obat:
Agen Antineoplastik
Panganggone Tezacaftor and Ivacaftor
Cystic Fibrosis
Pengobatan cystic fibrosis ing pasien ≥6 taun sing homozigot kanggo mutasi F508del ing gen CFTR utawa duwe paling sethithik 1 mutasi ing gen CFTR sing responsif marang obat kombinasi regimen.
Ditetepake obat yatim piatu dening FDA kanggo perawatan cystic fibrosis.
Yen genotipe pasien ora dingerteni, gunakake tes mutasi cystic fibrosis sing disetujoni FDA kanggo ndeteksi anané CFTR mutasi banjur diverifikasi kanthi urutan bidirectional nalika disaranake dening instruksi tes mutasi.
Pedoman paru Yayasan Cystic Fibrosis 2018 khusus ngarahake panggunaan modulator CFTR ing pasien karo cystic fibrosis. Tezacaftor/ivacaftor disetujoni sawise diterbitake pedoman, lan mulane ora ditangani.
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Carane nggunakake Tezacaftor and Ivacaftor
Umum
Skrining Pretreatment
Monitoring Pasien h4>
Administrasi
Oral Administration
Administrasi oral karo panganan sing ngandhut lemak (contone, endhog, keju, kacang-kacangan, susu wutuh, daging, panganan sing disiapake karo mentega utawa lenga. ) kanggo nambah panyerepan sistemik obat.
Telepon tablet wutuh.
Dosis
Kasedhiya minangka kit sing ngemot 4 kertu blister mingguan 7 tablet sing ngemot 100 mg saka tezacaftor ing kombinasi tetep karo 150 mg saka ivacaftor copackaged karo 7 tablet ngemot 150 mg siji-entitas ivacaftor.
Uga kasedhiya minangka kit ngemot 4 kertu blister mingguan 7 tablet ngemot 50 mg saka tezacaftor ing tetep kombinasi karo 75 mg ivacaftor sing dikemas bebarengan karo 7 tablet sing ngemot 75 mg ivacaftor entitas tunggal.
Pasien Pediatrik
Fibrosis Kistik OralBocah umur 6 nganti <12 taun kanthi bobot <30 kg : Tezacaftor 50 mg/ivacaftor 75 mg sapisan dina ing wayah esuk lan ivacaftor siji-entitas 75 mg sapisan dina ing wayah sore (dijupuk kira-kira 12 jam saben dina).
Bocah umur 6 nganti <12 taun bobote ≥30 kg: Tezacaftor 100 mg/ivacaftor 150 mg sapisan dina ing wayah esuk lan ivacaftor siji-siji 150 mg sapisan dina ing wayah sore (dijupuk kira-kira 12 jam).
p>Bocah ≥12 taun: Tezacaftor 100 mg/ivacaftor 150 mg sapisan dina ing wayah esuk lan ivacaftor siji-siji 150 mg sapisan dina ing wayah sore (dijupuk kira-kira 12 jam saben dina).
Panyesuaian dosis perlu nalika digunakake bebarengan karo inhibitor CYP3A sing moderat utawa kuwat.
Modifikasi Dosis kanggo Panggunaan Inhibitor CYP3A Moderat utawa Kuat OralPasien bocah umur 6 nganti <12 taun kanthi bobot <30 kg nampa inhibitor CYP3A moderat (contone, eritromisin, flukonazol): ngatur tezacaftor 50 mg / ivacaftor 75 mg tablet kombinasi tetep sepisan saben dina lan ivacaftor siji-entitas 75 mg sapisan saben dina, ing dina alternatif ing enjing. Aja menehi dosis sore ivacaftor entitas tunggal 75 mg ing pasien kasebut.
Pasien pediatrik 6 nganti <12 taun kanthi bobot ≥30 kg sing nampa inhibitor CYP3A moderat ( contone, eritromisin, flukonazol): ngaturake 100 mg/ivacaftor 150 mg tablet kombinasi tetep sapisan saben dina lan ivacaftor siji-entitas 150 mg sapisan dina, ing dina sulih ing wayah esuk. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Pasien pediatrik ≥12 taun nampa inhibitor CYP3A moderat (contone, erythromycin, fluconazole) : ngatur tezacaftor 100 mg/ivacaftor 150 mg tablet kombinasi tetep sapisan saben dina lan ivacaftor siji-entitas 150 mg sapisan dina, ing dina sulih ing wayah esuk. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Pasien pediatrik 6 nganti <12 taun kanthi bobot <30 kg sing nampa inhibitor CYP3A sing kuat ( contone, clarithromycin, itraconazole, ketokonazol, posaconazole, telitromisin, vorikonazol): ngatur tezacaftor 50 mg/ivacaftor 75 mg tablet kombinasi tetep kaping pindho saben minggu, kira-kira 3-4 dina. Aja menehi dosis sore ivacaftor entitas tunggal 75 mg ing pasien kasebut.
Pasien pediatrik 6 nganti <12 taun kanthi bobot ≥30 kg sing nampa inhibitor CYP3A sing kuat ( contone, clarithromycin, itraconazole, ketokonazol, posaconazole, telitromisin, vorikonazol): ngatur tezacaftor 100 mg/ivacaftor 150 mg tablet kombinasi tetep kaping pindho saben minggu, kira-kira 3-4 dina. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Pasien pediatrik ≥12 taun sing nampa inhibitor CYP3A sing kuat (contone, clarithromycin, itraconazole, ketokonazol, posaconazole, telitromisin, vorikonazol): ngaturake tezacaftor 100 mg/ivacaftor 150 mg tablet kombinasi tetep kaping pindho saben minggu, kira-kira 3-4 dina. Aja menehi dosis sore ivacaftor 150 mg ing pasien kasebut.
Dewasa
Fibrosis Cystic OralTezacaftor 100 mg/ivacaftor 150 mg sapisan dina ing wayah esuk lan siji- entitas ivacaftor 150 mg sapisan saben dina ing wayah sore (dijupuk kira-kira 12 jam).
Panyesuaian dosis perlu yen digunakake bebarengan karo inhibitor CYP3A moderat utawa kuwat.
Modifikasi Dosis kanggo Panggunaan Inhibitor CYP3A Moderat utawa Kuat OralPenggunaan bebarengan inhibitor CYP3A moderat (contone, eritromisin, flukonazol): atur tezacaftor 100 mg/ivacaftor 150 mg tablet kombinasi tetep sepisan saben dina lan ivacaftor siji-entitas 150 mg sapisan saben dina liyane, diwenehake ing dina sulih ing wayah esuk. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg.
Penggunaan bebarengan inhibitor CYP3A sing kuat (contone, clarithromycin, itraconazole, ketokonazol, posaconazole, telitromisin, vorikonazol) : ngaturake tezacaftor 100 mg/ivacaftor 150 mg tablet kombinasi tetep kaping pindho saben minggu, kira-kira 3-4 dina. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg.
Populasi Khusus
Gangguan Hepatik
Gangguan hepatik ringan (kelas Anak-Pugh A): Penyesuaian dosis ora perlu.
Pasien 6 nganti <12 taun kanthi bobot <30 kg kanthi gangguan hepatik moderat (Child-Pugh kelas B): tezacaftor 50 mg/ivacaftor 75 mg sapisan saben esuk. Aja menehi dosis sore ivacaftor entitas tunggal 75 mg ing pasien kasebut.
Pasien 6 nganti <12 taun kanthi bobote ≥30 kg kanthi gangguan ati moderat (kelas Child-Pugh B) : tezacaftor 100 mg/ivacaftor 150 mg sapisan dina ing wayah esuk. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Pasien ≥12 taun kanthi gangguan ati moderat (kelas Child-Pugh B): tezacaftor 100 mg / ivacaftor 150 mg sapisan dina ing wayah esuk. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Pasien umur 6 nganti <12 taun kanthi bobot <30 kg kanthi gangguan hepatik abot (kelas Child-Pugh C) : tezacaftor 50 mg/ivacaftor 75 mg sapisan dina ing wayah esuk utawa kurang asring. Aja menehi dosis sore ivacaftor entitas tunggal 75 mg ing pasien kasebut.
Pasien 6 nganti <12 taun kanthi bobote ≥30 kg kanthi gangguan hepatik abot (kelas Child-Pugh C) : tezacaftor 100 mg/ivacaftor 150 mg sapisan dina ing wayah esuk utawa kurang asring. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Pasien ≥12 taun kanthi gangguan hepatik abot (kelas Child-Pugh C): tezacaftor 100 mg/ivacaftor 150 mg sapisan dina ing wayah esuk utawa kurang asring. Aja menehi dosis sore ivacaftor entitas tunggal 150 mg ing pasien kasebut.
Gangguan Ginjal
Gangguan ginjel entheng nganti sedheng: Ora perlu nyetel dosis.
Gagal ginjel abot utawa penyakit ginjel tahap pungkasan (ESRD): Disaranake ati-ati.
Pasien Geriatri
Saiki ora ana rekomendasi dosis khusus.
Pènget
Kontraindikasi
Pènget/PanandhapEfek Hepatik
Konsentrasi ALT utawa AST sing luwih dhuwur dilapurake.
Kaji konsentrasi ALT lan AST serum sadurunge miwiti terapi, saben 3 sasi sajrone taun pisanan, lan saben taun sabanjure. Ing pasien kanthi riwayat kenaikan ALT utawa AST, nimbang pemantauan sing luwih kerep. Ngawasi kanthi rapet pasien sing ngembangake konsentrasi ALT, AST, utawa bilirubin sing tambah nganti ora normal.
Interupsi terapi ing pasien kanthi kenaikan ALT utawa AST> 5 kali ULN utawa ing wong kanthi peningkatan ALT utawa AST> 3 kali. ULN nalika digandhengake karo konsentrasi bilirubin sing dhuwur> 2 kali ULN. Sawise resolusi tingkat ALT utawa AST, nimbang keuntungan lan risiko nerusake terapi.
Interaksi karo Inducers CYP3A
Panganggone bebarengan karo inducers CYP3A sing kuwat nyuda paparan sistemik ivacaftor lan bisa nyuda paparan tezacaftor; nyuda eksposur bisa nyuda khasiat terapeutik. Panggunaan bebarengan karo inducer CYP3A sing kuat ora dianjurake. (Deleng Interaksi.)
Efek Okular
Kekeruhan lensa okuler (ora ana alam bawaan) sing dilapurake ing pasien pediatrik sing nampa terapi kombinasi tezacaftor/ivacaftor utawa monoterapi ivacaftor. Pemeriksan ophthalmologic dhasar lan tindak lanjut dianjurake kanggo pasien pediatrik.
Populasi Tertentu
KandhutanData winates kasedhiya babagan panggunaan terapi kombinasi tezacaftor/ivacaftor utawa komponen individu ing wanita ngandhut. Bukti teratogenisitas utawa efek samping ing perkembangan janin sing ora diamati ing kewan sing nampa tezacaftor utawa ivacaftor. Ora ana data kewan sing kasedhiya kanthi nggunakake tezacaftor lan ivacaftor bebarengan. Transfer plasenta saka tezacaftor diamati ing tikus ngandhut; transfer plasenta saka ivacaftor diamati ing tikus ngandhut lan terwelu.
LaktasiDistribusi menyang susu ing tikus; ora dingerteni manawa disebarake menyang susu manungsa. Coba keuntungan pangembangan lan kesehatan saka nyusoni lan pentinge klinis terapi kanggo wanita nalika mutusake manawa kudu ati-ati utawa mandheg nyusoni. Efek saka tezacaftor/ivacaftor ing kombinasi tetep ing bayi sing nyusoni utawa produksi susu ora dingerteni.
Panggunaan PediatrikKeamanan lan khasiat ora ditetepake ing pasien pediatrik <6 taun.
Efikasi kanggo pasien 6 nganti <12 taun sing diekstrapolasi saka khasiat asil ing pasien ≥12 taun kanthi dhukungan saka analisis farmakokinetik populasi sing nuduhake eksposur obat sing padha ing pasien umur 6 nganti <12 taun lan umur ≥12 taun. Profil safety ing pasien 6 nganti <12 taun padha karo sing diamati ing pasien ≥12 taun.
Panggunaan GeriatrikPengalaman sing ora cukup ing pasien ≥65 taun kanggo nemtokake manawa pasien geriatrik nanggapi beda karo wong diwasa sing luwih enom.
Gangguan HepatikGangguan hepatik entheng (kelas Anak-Pugh A): Efek babagan farmakokinetik sing ora diteliti; pangaturan dosis ora perlu.
Gagal ati moderat (Child-Pugh kelas B): Tambah cahya; nyuda dosis dianjurake.
Gagal ati sing abot (Child-Pugh kelas C): Efek ing farmakokinetik sing ora diteliti, nanging tambah akeh eksposur. Gunakake kanthi ati-ati lan ing dosis suda sawise nimbang risiko lan keuntungan saka terapi.
Gagal GinjalOra diteliti ing pasien kanthi gangguan ginjel moderat utawa abot utawa ing wong sing duwe ESRD.
Anteng utawa sedheng. Gagal ginjel: Ora perlu nyetel dosis.
Gagal ginjel abot (Clcr ≤30 mL/menit) utawa ESRD: Gunakake kanthi ati-ati.
Efek Sabar sing Umum
Efek sing ora becik (≥3% pasien): sirah, mual, kongesti sinus, pusing.
Apa obatan liyane bakal mengaruhi Tezacaftor and Ivacaftor
Tezacaftor minangka substrat isoenzim CYP3A (contone, CYP3A4, CYP3A5), transportasi P-glikoprotein (P-gp), protein tahan kanker payudara (BCRP), lan polipeptida pengangkut anion organik (OATP) 1B1.
Ivacaftor minangka substrat sensitif CYP3A. In vitro, ivacaftor duweni potensi kanggo nyandhet CYP3A lan P-gp, lan uga bisa nyandhet CYP2C9.
Obat sing Ngaruhi utawa Dimetabolisme dening Enzim Mikrosomal Hepatik
Substrat CYP3A: Ora perlu penyesuaian dosis.
Inhibitor CYP3A sing kuat: Interaksi farmakokinetik (bisa tambah eksposur tezacaftor lan ivacaftor). Ngurangi dosis dadi tezacaftor 100 mg/ivacaftor 150 mg ing kombinasi tetep kaping pindho saben minggu, kira-kira 3-4 dina. Aja menehi ivacaftor entitas tunggal 150 mg.
Inhibitor CYP3A moderat: Interaksi farmakokinetik (bisa tambah eksposur tezacaftor lan ivacaftor). Ing wong diwasa, bocah-bocah ≥12 taun, lan bocah-bocah umur 6 nganti <12 taun kanthi bobote ≥30 kg, nyuda dosis dadi tezacaftor 100 mg / ivacaftor 150 mg kanthi kombinasi tetep saben dina kanthi kombinasi karo ivacaftor 150 mg siji-entitas sapisan saben dina liyane, diwenehi ing dina sulih. Aja menehi dosis sore saka ivacaftor entitas tunggal 150 mg ing pasien kasebut. Ing bocah-bocah umur 6 nganti <12 taun sing bobote <30 kg, ngurangi dosis dadi tezacaftor 50 mg / ivacaftor 75 mg ing kombinasi tetep sapisan saben dina kanthi kombinasi karo ivacaftor entitas tunggal 75 mg sapisan saben dina liyane, diwenehi dina alternatif. Aja menehi dosis sore ivacaftor entitas tunggal 75 mg ing pasien kasebut.
Inducer CYP3A sing kuat: Interaksi farmakokinetik (mudhun paparan ivacaftor; nyuda eksposur tezacaftor samesthine). Ora dianjurake kanggo nggunakake bebarengan.
Obat sing kena pengaruh P-glikoprotein Transport
Substrat P-gp: Interaksi farmakokinetik (bisa tambah pajanan, efek terapeutik sing suwe, utawa tambah risiko efek samping saka obat kasebut. obat substrat). Gunakake substrat P-gp kanthi indeks terapeutik sing sempit bebarengan kanthi ati-ati; ngawasi pasien kanthi tepat.
Obat Spesifik
Obat utawa Pangan
Interaksi
Komentar
Anticonvulsants (Carbamazepine, phenobarbital, phenytoin)
Bisa ngurangi paparan tezacaftor lan ivacaftor lan ngurangi khasiat tezacaftor/ivacaftor
Panganggone bebarengan ora dianjurake
Anti jamur , azoles (flukonazol, itrakonazol, ketokonazol, posakonazol, vorikonazol)
Itrakonazol: Panggunaan bebarengan karo tezacaftor/ivacaftor ngasilake 4- lan 15,6 kali lipat AUC tezacaftor lan ivacaftor, masing-masing
Flukonazol: Panggunaan bebarengan karo ivacaftor nyebabake peningkatan AUC ivacaftor kaping telu; nggunakake bebarengan karo tezacaftor bisa nambah paparan tezacaftor kira-kira kaping pindho
Itraconazole, ketoconazole, posaconazole, vorikonazol: Ing wong diwasa, bocah-bocah ≥12 taun, lan bocah-bocah umur 6 nganti <12 taun kanthi bobote ≥30 kg, ngurangi dosis kanggo tezacaftor 100 mg / ivacaftor 150 mg kaping pindho saben minggu, kira-kira 3-4 dina (aja menehi dosis sore saka ivacaftor entitas tunggal 150 mg); ing bocah-bocah umur 6 nganti <12 taun kanthi bobot <30 kg, nyuda dosis dadi tezacaftor 50 mg / ivacaftor 75 mg kaping pindho saben minggu, kira-kira 3-4 dina (ora menehi dosis sore saka ivacaftor entitas tunggal 75 mg) p>
Fluconazole: Ing wong diwasa, bocah-bocah umur ≥12 taun, lan bocah-bocah umur 6 nganti <12 taun kanthi bobote ≥30 kg, ngurangi dosis dadi tezacaftor 100 mg/ivacaftor 150 mg sapisan dina lan ivacaftor siji-entitas 150 mg sapisan saben dina liyane, diwenehi dina sulih (ora ngatur dosis sore ivacaftor 150 mg siji-entitas); ing bocah-bocah umur 6 nganti <12 taun sing bobote <30 kg, nyuda dosis dadi tezacaftor 50 mg / ivacaftor 75 mg kanthi kombinasi tetep sapisan saben dina kanthi kombinasi karo ivacaftor entitas tunggal 75 mg sapisan dina, diwenehi dina alternatif ( aja menehi dosis sore ivacaftor entitas tunggal 75 mg)
Antimycobacterial (rifabutin, rifampisin)
Rifabutin: Kemungkinan nyuda eksposur tezacaftor lan ivacaftor lan nyuda khasiat tezacaftor/ivacaftor
Rifampisin: Ngurangi paparan ivacaftor nganti 89%; nyuda cahya tezacaftor uga samesthine; bisa nyuda khasiat tezacaftor/ivacaftor
Panganggone bebarengan ora dianjurake
Ciprofloxacin
Ora ana efek klinis penting ing paparan tezacaftor utawa ivacaftor
Dosis pangaturan ora dibutuhake
Digoxin
Tambahan paparan digoxin; kemungkinan efek terapeutik sing berpanjangan saka digoxin utawa tambah risiko efek samping sing gegandhengan karo digoxin
Gunakake kanthi ati-ati lan ngawasi kanthi tepat
Eritromisin
Kamungkinan tambah paparan tezacaftor lan ivacaftor
Ing wong diwasa, bocah-bocah umur ≥12 taun, lan bocah-bocah umur 6 nganti <12 taun kanthi bobote ≥30 kg, nyuda dosis dadi tezacaftor 100 mg / ivacaftor 150 mg sapisan dina lan ivacaftor entitas tunggal 150 mg saben dina. dina liyane, diwenehi dina sulih (ora ngatur dosis sore ivacaftor entitas tunggal 150 mg); ing bocah-bocah umur 6 nganti <12 taun sing bobote <30 kg, nyuda dosis dadi tezacaftor 50 mg / ivacaftor 75 mg kanthi kombinasi tetep sapisan saben dina kanthi kombinasi karo ivacaftor entitas tunggal 75 mg sapisan saben dina liyane, diwenehi dina alternatif ( aja menehi dosis sore ivacaftor entitas tunggal 75 mg)Estrogen lan progestin
Etinil estradiol lan norethindrone: Ora ana efek sing signifikan ing paparan etinil estradiol, norethindrone, tezacaftor, utawa ivacaftor
Kontrasepsi hormonal: Panggunaan bebarengan ora samesthine kanggo mengaruhi khasiat kontrasepsi hormonal
Jus jeruk bali utawa jeruk bali
Kamungkinan tambah paparan tezacaftor lan ivacaftor
Aja nggunakake bebarengan
Imunosupresan (siklosporin, everolimus, sirolimus, tacrolimus)
Kamungkinan tambah paparan imunosupresan, efek terapeutik sing suwe, utawa tambah risiko efek samping sing ana gandhengane karo imunosupresan
Gunakake bebarengan kanthi ati-ati; ngawasi pasien kanthi bener
Pitavastatin
Ora ana efek sing signifikan ing paparan pitavastatin
St. John's wort (Hypericum perforatum)
Kamungkinan nyuda eksposur tezacaftor lan ivacaftor lan nyuda khasiat tezacaftor/ivacaftor
Panganggone bebarengan ora dianjurake
Sulfonilurea
Glimepiride, glipizide: Kemungkinan tambah paparan glimepiride utawa glipizide (substrat CYP2C9)
Gunakake kanthi ati-ati
Warfarin
Kamungkinan tambah paparan warfarin (CYP2C9 landasan)
Monitor INR
Disclaimer
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