Relugolix, Estradiol, and Norethindrone Acetate
Jeneng merek: Myfembree
Kelas obat:
Agen Antineoplastik
Panganggone Relugolix, Estradiol, and Norethindrone Acetate
Relugolix, estradiol, lan norethindrone acetate nduweni kegunaan ing ngisor iki:
Relugolix, estradiol, lan norethindrone acetate minangka kombinasi saka relugolix, antagonis reseptor gonadotropin-releasing hormone (GnRH), estradiol, estrogen , lan norethindrone acetate, progestin, lan dituduhake kanggo ngatur pendarahan menstruasi abot sing ana hubungane karo leiomioma uterine (fibroid) ing wanita premenopausal.
Relugolix, estradiol, lan norethindrone acetate nduweni watesan ing ngisor iki:
Panganggone relugolix, estradiol, lan norethindrone acetate kudu diwatesi nganti 24 sasi amarga risiko mundhut balung terus, sing bisa uga ora bisa dibalèkaké.
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Carane nggunakake Relugolix, Estradiol, and Norethindrone Acetate
Umum
Relugolix, estradiol, lan norethindrone acetate kasedhiya ing wangun dosis lan kekuatan:
Tablet: kombinasi dosis tetep sing ngemot relugolix 40 mg, estradiol 1 mg, lan norethindrone asetat 0,5 mg
Dosis
Pancen penting panyedhiya label pabrikan kudu dikonsultasi kanggo informasi sing luwih rinci babagan dosis lan administrasi obat iki. Ringkesan dosis:
Wong diwasa
Dosis lan AdministrasiPènget
Kontraindikasi
Gagal utawa penyakit hepatik sing dikenal.
Pènget/PanandhapGangguan Thromboembolic lan Kedadean Vaskular
Relugolix, estradiol, lan norethindrone acetate dikontraindikasi ing wanita sing duwe riwayat kelainan trombotik utawa tromboembolik saiki lan ing wanita kanthi risiko tambah kanggo kedadeyan kasebut.
Mateni relugolix, estradiol, lan norethindrone acetate sanalika yen ana trombotik arteri utawa vena, kardiovaskuler, utawa serebrovaskular kedadeyan utawa dicurigai. Mungkasi relugolix, estradiol, lan norethindrone acetate paling sethithik 4 nganti 6 minggu sadurunge operasi sing gegandhèngan karo risiko tromboembolisme sing luwih dhuwur, utawa sajrone wektu imobilisasi sing dawa, yen bisa.
Mateni relugolix, estradiol, lan norethindrone asetat langsung yen ana mundhut sebagean utawa lengkap sing ora bisa dijelasake kanthi tiba-tiba, proptosis, diplopia, papilledema, utawa lesi pembuluh darah retina lan ngevaluasi trombosis vena retina amarga wis dilaporake ing pasien sing nampa estrogen lan progestin.
Estrogen lan progestin kombinasi, kalebu komponen estradiol / norethindrone asetat saka relugolix, estradiol, lan norethindrone asetat, nambah risiko kelainan thrombotic utawa thromboembolic, kalebu pulmonary embolism (PE), deep-vein thrombosis (DVT), stroke, lan infark miokard, utamane ing wanita kanthi risiko dhuwur kanggo acara kasebut. Umumé, risiko paling gedhé ing antarane wanita sing umure luwih saka 35 taun sing ngrokok, lan wanita kanthi hipertensi sing ora bisa dikontrol, dislipidemia, penyakit pembuluh darah, utawa obesitas.
Ing uji klinis sing dikontrol plasebo Fase 3 ing 1066 wanita sing diobati. karo relugolix, estradiol, lan norethindrone acetate kanggo indikasi liyane, 2 acara thromboembolic (DVT lan PE) dumadi ing 1 wanita kanthi faktor risiko obesitas lan cedera lutut sadurunge lan siji kasus dilaporake kanggo wanita sing diobati karo monoterapi relugolix ing periode pasca pemasaran. .
Bone Loss
Relugolix, estradiol, lan norethindrone acetate dikontraindikake ing wanita sing duwe osteoporosis sing dikenal. Coba manfaat lan risiko perawatan relugolix, estradiol, lan norethindrone acetate ing pasien kanthi riwayat fraktur trauma rendah utawa faktor risiko osteoporosis utawa mundhut balung, kalebu njupuk obat-obatan sing bisa nyuda kapadhetan mineral balung (BMD) (contone, sistemik). utawa kortikosteroid inhalasi kronis, antikonvulsan, utawa panggunaan kronis inhibitor pompa proton).
Assessment BMD dening absorptiometry sinar-X energi ganda (DXA) dianjurake ing awal lan sacara periodik sakwise. Coba mandhegake relugolix, estradiol, lan norethindrone acetate yen risiko sing ana gandhengane karo mundhut balung ngluwihi manfaat potensial perawatan. Sanajan efek suplementasi karo kalsium lan vitamin D ora diteliti, suplemen kasebut kanggo pasien kanthi asupan diet sing ora nyukupi bisa uga migunani. Relugolix, estradiol, lan norethindrone acetate bisa nyebabake nyuda BMD ing sawetara pasien. Mundhut BMD bisa uga luwih gedhe kanthi nambah durasi panggunaan lan bisa uga ora bisa dibatalake sawise mandheg perawatan. Dampak BMD nyuda kesehatan balung jangka panjang lan risiko patah tulang ing wanita premenopausal ora dingerteni.
Ing uji klinis Fase 3, wanita sing diobati karo relugolix, estradiol, lan norethindrone acetate nganti 52 minggu wis penurunan BMD spine lumbar 0,8%.
Malignansi sensitif hormon
Relugolix, estradiol, lan norethindrone acetate dikontraindikake ing wanita sing duwe riwayat malignancy sensitif hormon (contone, kanker payudara) lan wanita kanthi risiko tambah hormon- malignancies sensitif. Mungkasi relugolix, estradiol, lan norethindrone acetate yen didiagnosa ganas sensitif hormon.
Tindakan pengawasan miturut standar perawatan kayata pemeriksaan payudara lan mamografi, dianjurake. Panganggone estrogen piyambak utawa estrogen plus progestin wis dilapurake nyebabake paningkatan mammogram sing ora normal sing mbutuhake evaluasi luwih lanjut.
Depresi, Gangguan Mood, lan Ide Bunuh Diri
Evaluasi kanthi cepet pasien kanthi owah-owahan swasana ati lan gejala depresi, kalebu sakcepete sawise miwiti perawatan, kanggo nemtokake manawa risiko terapi terus karo relugolix, estradiol, lan norethindrone acetate ngluwihi keuntungan. Pasien sing ngalami depresi, kuatir, utawa owah-owahan swasana ati sing anyar utawa saya tambah kudu dirujuk menyang profesional kesehatan mental sing cocog. Nasehati pasien supaya njaluk perhatian medis langsung kanggo ide lan prilaku bunuh diri. Evaluasi maneh keuntungan lan risiko nerusake relugolix, estradiol, lan norethindrone acetate yen kedadeyan kasebut.
Ing uji klinis sing dikontrol plasebo Fase 3, dibandhingake karo plasebo, proporsi wanita sing diobati karo relugolix, estradiol luwih akeh. , lan norethindrone acetate nglapurake depresi (kalebu depresi, owah-owahan swasana ati, lan swasana ati sing depresi) (2.4% vs. 0.8%), irritability (2.4% vs. 0%), lan kuatir (1.2% vs. 0.8%). Gagasan bunuh diri dumadi ing wanita sing diobati karo relugolix, estradiol, lan norethindrone acetate ing uji klinis sing dikontrol plasebo sing ditindakake kanggo indikasi sing beda.
Gangguan Hepatik lan Peningkatan Transaminase
Relugolix, estradiol, lan norethindrone acetate dikontraindikasi ing pasien sing duwe gangguan utawa penyakit hepatik sing dikenal. Hormon steroid bisa uga kurang metabolisme ing pasien sing duwe fungsi ati sing cacat.
Anjurake wanita supaya cepet golek perawatan medis kanggo gejala utawa pratandha sing bisa nggambarake ciloko ati, kayata jaundice utawa nyeri weteng sisih ndhuwur. Kelainan tes ati akut bisa uga mbutuhake mandheg saka relugolix, estradiol, lan norethindrone asetat nganti tes ati bali menyang normal lan panyebab relugolix, estradiol, lan norethindrone asetat ora kalebu.
Ing Fase 3 klinis sing dikontrol plasebo Uji coba, elevasi (≥3 kaping wates ndhuwur normal [ULN] saka kisaran referensi) ing alanine aminotransferase (ALT) dumadi ing 0,4% (1/254) wanita sing diobati karo relugolix, estradiol, lan norethindrone acetate dibandhingake karo ora. elevasi ing wanita sing diobati plasebo. Peningkatan ≥3 kaping ULN ing aspartate aminotransferase (AST) dumadi ing 0,8% (2/254) wanita sing diobati karo relugolix, estradiol, lan norethindrone asetat dibandhingake karo 0,4% (1/256) wanita sing diobati plasebo. Ora ana pola ing wektu wiwitan paningkatan transaminase ati iki diidentifikasi.
Penyakit Kandung Empedu utawa Riwayat Jaundice Kolestatik
Stop relugolix, estradiol, lan norethindrone acetate yen ana pratandha utawa gejala penyakit kandung empedu utawa jaundice. Kanggo wanita kanthi riwayat jaundice kolestatik sing ana gandhengane karo panggunaan estrogen sing kepungkur utawa nalika meteng, evaluasi risiko-manfaat terapi terus. Panaliten ing antarane pangguna estrogen nuduhake risiko relatif cilik kanggo ngembangake penyakit kandung empedu.
Peningkatan Tekanan Darah
Relugolix, estradiol, lan norethindrone acetate dikontraindikasi ing wanita kanthi hipertensi sing ora bisa dikontrol. Kanggo wanita kanthi hipertensi sing dikontrol kanthi apik, terus ngawasi tekanan getih lan mungkasi relugolix, estradiol, lan norethindrone acetate yen tekanan getih mundhak sacara signifikan.
Ing salah siji saka rong uji klinis Fase 3 (Studi L1), luwih akeh. wanita ngalami reaksi salabetipun hipertensi anyar utawa worsening karo relugolix, estradiol, lan norethindrone asetat dibandhingake placebo (7% vs. 0,8%).
Owah-owahan ing Pola Pendarahan Menstruasi lan Kemampuan Suda kanggo Ngenali Kandhutan
Singkirake meteng sadurunge miwiti relugolix, estradiol, lan norethindrone acetate. Mulai relugolix, estradiol, lan norethindrone acetate sakcepete sawise wiwitan haid nanging ora luwih saka 7 dina sawise haid diwiwiti. Yen relugolix, estradiol, lan norethindrone acetate diwiwiti mengko ing siklus menstruasi, getihen sing ora teratur lan / utawa abot bisa kedadeyan. Wanita sing njupuk relugolix, estradiol, lan norethindrone acetate bisa ngalami amenore utawa nyuda jumlah, intensitas, utawa durasi pendarahan menstruasi, sing bisa nundha kemampuan kanggo ngenali meteng. Tindakake tes meteng yen dicurigai meteng lan mandhegake relugolix, estradiol, lan norethindrone acetate yen meteng dikonfirmasi.
Anjurake wanita sing duwe potensi reproduksi kanggo nggunakake kontrasepsi non-hormonal sing efektif sajrone perawatan karo relugolix, estradiol, lan norethindrone acetate lan seminggu sawise dosis pungkasan. Aja nggunakake kontrasepsi hormonal kanthi relugolix, estradiol, lan norethindrone asetat. Panganggone kontrasepsi hormonal sing ngandhut estrogen bisa ningkatake tingkat estrogen sing bisa nambah risiko efek samping sing ana gandhengane karo estrogen lan nyuda khasiat relugolix, estradiol, lan norethindrone acetate.
Risiko Mundhut Kandhutan Awal
Relugolix, estradiol, lan norethindrone acetate dikontraindikasi kanggo nggunakake nalika meteng. Adhedhasar temuan saka studi kewan lan mekanisme tumindake, relugolix, estradiol, lan norethindrone acetate bisa nyebabake mundhut awal meteng. Nanging, ing terwelu lan tikus, ora ana malformasi janin ing tingkat dosis sing dites sing digandhengake karo paparan relugolix kira-kira setengah lan kira-kira 300 kaping eksposur ing wanita ing dosis manungsa sing disaranake.
Uterine Fibroid Prolapse or Expulsion
Anjurake wanita kanthi fibroid uterine submucosal sing dikawruhi utawa dicurigai babagan kemungkinan prolaps utawa ekspulsi fibroid uterine lan pitunjuk menyang dokter yen ana pendarahan lan/utawa kram sing abot nalika lagi. diobati karo relugolix, estradiol, lan norethindrone asetat. Ing uji klinis sing dikontrol plasebo Fase 3, prolaps fibroid uterine lan ekspulsi fibroid uterus kacarita ing wanita sing diobati karo relugolix, estradiol, lan norethindrone acetate.
Alopecia
Coba mandhegake relugolix, estradiol, lan norethindrone acetate yen rambut rontog dadi kuwatir.
Ing uji klinis sing dikontrol plasebo Fase 3, luwih akeh wanita ngalami alopecia, rambut rontog. , lan rambut tipis (3,5%) karo relugolix, estradiol, lan norethindrone asetat, dibandhingake karo plasebo (0,8%). Ing 3 saka 11 wanita sing kena pengaruh sing diobati karo relugolix, estradiol, lan norethindrone acetate ing uji klinis Fase 3, alopecia kacarita minangka moderat. Kanggo siji wanita sing diobati karo relugolix, estradiol, lan norethindrone acetate ing uji coba ekstensi, alopecia minangka alasan kanggo mungkasi perawatan.
Ora ana pola rambut rontog sing diterangake. Mayoritas wanita sing kena pengaruh ngrampungake panliten kasebut kanthi kerontokan rambut sing dilaporake. Apa rambut rontok bisa dibalik ora dingerteni.
Efek ing Karbohidrat lan Metabolisme Lipid
Pemantauan sing luwih kerep ing wanita sing diobati karo relugolix, estradiol, lan norethindrone asetat kanthi prediabetes lan diabetes bisa uga dibutuhake. Relugolix, estradiol, lan norethindrone acetate bisa nyuda toleransi glukosa lan nyebabake konsentrasi glukosa getih mundhak.
Pantau tingkat lipid lan nimbang nyetop relugolix, estradiol, lan norethindrone acetate yen hiperkolesterolemia utawa hipertrigliseridemia saya tambah parah. Ing wanita kanthi hipertrigliseridemia sing wis ana, terapi estrogen bisa uga ana gandhengane karo kenaikan tingkat trigliserida sing nyebabake pankreatitis. Panganggone relugolix, estradiol, lan norethindrone acetate digandhengake karo paningkatan kolesterol total lan kolesterol lipoprotein kapadhetan rendah (LDL-C).
Efek ing Asil Laboratorium Liyane
Pasien hipotiroidisme lan hypoadrenalism mbutuhake dosis hormon tiroid utawa terapi pengganti kortisol sing luwih dhuwur.
Panganggone kombinasi estrogen lan progestin bisa ningkatake konsentrasi serum. protein pengikat (contone, globulin pengikat tiroid, globulin pengikat kortikosteroid), sing bisa nyuda tingkat hormon tiroid utawa kortikosteroid gratis.
Panganggone estrogen lan progestin uga bisa mengaruhi tingkat pengikat hormon seks. globulin lan faktor koagulasi.
Reaksi Hipersensitivitas
Relugolix, estradiol, lan norethindrone acetate dikontraindikake ing wanita kanthi riwayat reaksi hipersensitivitas kanggo relugolix utawa komponen relugolix, estradiol, lan norethindrone acetate. Langsung mateni relugolix, estradiol, lan norethindrone acetate yen ana reaksi hipersensitivitas.
Populasi Tertentu
KandhutanRegistry Paparan Kandhutan: Ana registri paparan kandhutan sing ngawasi asil meteng ing wanita sing kena relugolix, estradiol, lan norethindrone acetate nalika meteng. Wanita ngandhut sing kena relugolix, estradiol, lan norethindrone acetate lan panyedhiya kesehatan disaranake nelpon Myfembree Pregnancy Exposure Registry ing 1-(855) 428-0707.
Ringkesan Risiko: Relugolix, estradiol, lan norethindrorethindro. wis contraindicated ing meteng. Adhedhasar temuan saka studi kewan lan mekanisme tumindake, relugolix, estradiol, lan norethindrone acetate bisa nyebabake mundhut awal meteng. Mungkasi relugolix, estradiol, lan norethindrone acetate yen meteng ana sajrone perawatan.
Data manungsa sing winates kanthi nggunakake relugolix, estradiol, lan norethindrone acetate ing wanita ngandhut ora cukup kanggo ngevaluasi risiko sing ana gandhengane karo obat. cacat lair utama, keguguran, utawa asil ibu utawa janin sing ora becik.
Ing studi reproduksi kewan, administrasi oral relugolix ing terwelu sing ngandhut sajrone organogenesis nyebabake aborsi spontan lan mundhut sampah total ing paparan relugolix kira-kira setengah saka relugolix. maksimum dianjurake dosis manungsa (MRHD) 40 mg. Ing terwelu lan tikus, ora ana malformasi janin ing tingkat dosis sing dites sing digandhengake karo eksposur relugolix kira-kira setengah lan kira-kira 300 kaping eksposur ing wanita ing MRHD.
Studi epidemiologis lan meta-analisis. durung nemu risiko tambah saka cacat lair genital utawa non-genital (kalebu anomali jantung lan cacat pangurangan anggota awak) sawise paparan estrogen lan progestin sadurunge angen-angen utawa nalika awal meteng.
Estimasi latar mburi risiko utama cacat lair lan keguguran kanggo populasi sing dituduhake ora dingerteni. Ora ana data sing cukup kanggo nyimpulake manawa anané fibroid uterine nyuda kemungkinan nggayuh meteng utawa nambah risiko asil meteng sing ora becik. Kabeh meteng duwe risiko latar mburi cacat lair, mundhut, utawa asil salabetipun liyane. Ing populasi umum Amerika Serikat, kira-kira risiko latar mburi cacat lair utama lan keguguran ing kandhutan sing diakoni sacara klinis yaiku 2% nganti 4% lan 15% nganti 20%.
Data Kewan: Ing perkembangan embriofetal. sinau, administrasi oral relugolix kanggo terwelu meteng sajrone periode organogenesis (dina 6 nganti 18 meteng) nyebabake aborsi, mundhut sampah total, utawa nyuda jumlah janin sing urip kanthi dosis 9 mg / kg / dina (udakara setengah dosis). paparan manungsa ing dosis manungsa maksimal sing disaranake (MRHD) 40 mg saben dina, adhedhasar AUC). Ora ana malformasi sing gegandhengan karo perawatan sing diamati ing janin sing isih urip. Ora ana efek sing gegandhengan karo perawatan diamati ing 3 mg / kg / dina (udakara 0,1 kali MRHD) utawa luwih murah. Afinitas ikatan relugolix kanggo reseptor GnRH terwelu ora dingerteni.
Ing studi perkembangan embriofetal sing padha, administrasi oral relugolix kanggo tikus ngandhut sajrone periode organogenesis (dina 6 nganti 17 meteng) ora mengaruhi meteng. status utawa titik pungkasan janin ing dosis nganti 1000 mg / kg / dina (300 kaping MRHD), dosis ing ngendi keracunan ibu (mudhun bobot awak lan konsumsi pangan) diamati. Tingkat efek samping sing ora diamati (NOAEL) kanggo keracunan ibu yaiku 200 mg / kg / dina (86 kaping MRHD). Ing tikus, afinitas ikatan relugolix kanggo reseptor GnRH luwih saka 1000 kali luwih murah tinimbang ing manungsa, lan panliten iki nggambarake evaluasi target non-farmakologis relugolix nalika meteng. Ora ana malformasi sing gegandhengan karo perawatan sing diamati nganti 1000 mg / kg / dina.
Ing studi perkembangan sadurunge lan postnatal ing tikus ngandhut lan lactating, administrasi oral relugolix kanggo tikus nalika pungkasan meteng lan lactation (dina 6). saka gestation nganti dina 20 laktasi) ora duwe efek ing perkembangan sadurunge lan postnatal ing dosis nganti 1000 mg / kg / dina (300 kaping MRHD), dosis sing diamati keracunan ibu (efek ing bobot awak). NOAEL kanggo keracunan ibu yaiku 100 mg / kg / dina (34 kaping MRHD).
LaktasiRingkesan Resiko: Ora ana data babagan anané relugolix utawa metabolit ing susu manungsa, efek ing bayi sing nyusoni, utawa efek ing produksi susu. Relugolix dideteksi ing susu ing tikus lactating. Nalika obat ana ing susu kewan, kemungkinan obat kasebut ana ing susu manungsa.
Jumlah estrogen lan progestin sing bisa dideteksi wis diidentifikasi ing ASI wanita sing nampa terapi estrogen plus progestin lan bisa nyuda produksi susu ing wanita sing nyusoni. Pengurangan iki bisa kedadeyan kapan wae, nanging ora bisa kedadeyan nalika nyusoni wis ditemtokake.
Manfaat pangembangan lan kesehatan saka nyusoni kudu dianggep bebarengan karo kabutuhan klinis wanita kanggo relugolix, estradiol , lan norethindrone acetate lan efek saleh potensial ing anak sing disusui saka relugolix, estradiol, lan norethindrone asetat utawa saka kondisi ibu sing ndasari. kg relugolix radiolabeled ing dina 14 postpartum, relugolix lan/utawa metabolit sawijining ana ing susu ing konsentrasi nganti 10 kaping luwih dhuwur tinimbang ing plasma ing 2 jam sawise-dosis.
Badhak wadon lan Lanang Potensi ReproduksiBased babagan data kewan lan mekanisme tumindak, relugolix, estradiol, lan norethindrone acetate bisa nyebabake mundhut meteng awal yen relugolix, estradiol, lan norethindrone asetat diwenehake marang wanita ngandhut.
Tes Kandhutan: Relugolix, estradiol, lan norethindrone acetate bisa nundha kemampuan kanggo ngenali meteng amarga bisa nyuda intensitas, durasi, lan jumlah pendarahan menstruasi. Ngilangi meteng sadurunge miwiti perawatan karo relugolix, estradiol, lan norethindrone acetate. Tindakake tes meteng yen dicurigai meteng sajrone perawatan karo relugolix, estradiol, lan norethindrone acetate lan mandhegake perawatan yen meteng dikonfirmasi.
Kontrasepsi: Nasihat wanita sing duwe potensi reproduksi kanggo nggunakake kontrasepsi nonhormonal sing efektif sajrone perawatan karo relugolix, estradiol , lan norethindrone acetate lan kanggo 1 minggu sawise mandheg. Aja nggunakake kontrasepsi hormonal kanthi relugolix, estradiol, lan norethindrone asetat. Panganggone kontrasepsi hormonal sing ngandhut estrogen bisa ningkatake risiko efek samping sing gegandhengan karo estrogen lan bakal ngurangi khasiat relugolix, estradiol, lan norethindrone acetate.
Panggunaan PediatrikAman lan efektifitas relugolix, estradiol , lan norethindrone acetate ing pasien pediatrik durung ditetepake.
Gangguan HepatikRelugolix, estradiol, lan norethindrone acetate dikontraindikake ing wanita kanthi gangguan utawa penyakit hepatik. Panganggone estradiol (komponen obat) ing pasien kanthi gangguan hepatik diprakirakake bisa nambah paparan estradiol lan nambah risiko reaksi salabetipun sing gegandhengan karo estradiol.
Efek salabetipun sing umum
Reaksi salabetipun sing paling umum (insiden ≥3%) yaiku hot flush, hiperhidrosis utawa kringet wengi, getihen uterus, alopecia, lan libido mudhun.
Apa obatan liyane bakal mengaruhi Relugolix, Estradiol, and Norethindrone Acetate
Obat Spesifik
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