Peringatan Keamanan

Toxicity information regarding omaveloxolone is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as elevation in hepatic transaminases and B-Type natriuretic peptide (BNP), as well as lipid abnormalities.L45424 Symptomatic and supportive measures are recommended.

The carcinogenicity of omaveloxolone has not been evaluated. In a bacterial reverse mutation (Ames) assay, omaveloxolone showed negative results, while a chromosomal aberration assay in human peripheral blood lymphocytes showed positive results. Rats given 0, 1, 3, and 10 mg/kg/day of oral omaveloxolone had a higher incidence of pre- and post-implantation loss and resorptions, leading to a decrease in viable embryos at the highest dose. The no-effect dose (3 mg/kg/day) of omaveloxolone for fertility and reproductive function adverse effects was equivalent to an AUC of approximately 2 times the recommended human dose(150 mg/day).L45424

Omaveloxolone

DB12513

small molecule approved investigational

Deskripsi

Omaveloxolone (RTA-408) is a semisynthetic oleanane triterpenoid with antioxidant and anti-inflammatory properties.A257534,A257539 Omaveloxolone acts as an activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor that mitigates oxidative stress. In patients with Friedreich's ataxia, a genetic disease involving mitochondrial dysfunction, the Nrf2 pathway is impaired, and Nrf2 activity is lower. Therefore, the use of Nrf2 activators such as omaveloxolone represents a therapeutic advantage in this group of patients.A257529 In February 2023, omaveloxolone was approved by the FDA for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older.L45424 The EMA approved this drug the following year, in February 2024, for the same condition.L51654 The use of omaveloxolone for the treatment of conditions involving mitochondrial dysfunction and oxidative stress has also been evaluated.A257534,A257559

Struktur Molekul 2D

Berat 554.723
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Omaveloxolone has a terminal half-life of 57 hours.[L45424]
Volume Distribusi Omaveloxolone has an apparent volume of distribution of 7361 L.[L45424]
Klirens (Clearance) Omaveloxolone has an apparent plasma clearance of 109 L/hr.[L45424]

Absorpsi

Between 50 mg (0.33 times the recommended dosage) and 150 mg, the AUC of omaveloxolone increased in a dose-dependent and dose-proportional manner. However, at the same dose range, the Cmax increased in a less than dose-proportional manner in healthy fasted subjects. The median time to achieve peak plasma concentration was 7 to 14 hours. Compared to fasted conditions, the AUC0-inf and Cmax of omaveloxolone were 350% and 15% higher with a high-fat meal (800 to 1000 calories, with 150, 250, and 500 to 600 calories coming from protein, carbohydrate, and fat, respectively).L45424

Metabolisme

Omaveloxolone is mainly metabolized by CYP3A, although CYP2C8 and CYP2J2 play also a minor role.L45424

Rute Eliminasi

Omaveloxolone is mainly excreted in feces. In healthy subjects given a single oral dose of radiolabeled omaveloxolone (150 mg), about 92% and 0.1% of the dose were recovered in feces and urine, respectively. Approximately 91% of the omaveloxolone found in feces was recovered within 96 hours after administration.L45424

Interaksi Makanan

1 Data
  • 1. Take on an empty stomach. Take omaveloxolone capsules on an empty stomach at least 1 hour before eating. Compared to fasting conditions, a high-fat meal increased the Cmax and AUC by approximately 350% and 15%, respectively.

Interaksi Obat

861 Data
Nelfinavir The serum concentration of Omaveloxolone can be increased when it is combined with Nelfinavir.
Indinavir The serum concentration of Omaveloxolone can be increased when it is combined with Indinavir.
Terfenadine The serum concentration of Omaveloxolone can be increased when it is combined with Terfenadine.
Ritonavir The serum concentration of Omaveloxolone can be increased when it is combined with Ritonavir.
Voriconazole The serum concentration of Omaveloxolone can be increased when it is combined with Voriconazole.
Efavirenz The serum concentration of Omaveloxolone can be increased when it is combined with Efavirenz.
Ergotamine The serum concentration of Omaveloxolone can be increased when it is combined with Ergotamine.
Amprenavir The serum concentration of Omaveloxolone can be increased when it is combined with Amprenavir.
Delavirdine The serum concentration of Omaveloxolone can be increased when it is combined with Delavirdine.
Methimazole The serum concentration of Omaveloxolone can be increased when it is combined with Methimazole.
Conivaptan The serum concentration of Omaveloxolone can be increased when it is combined with Conivaptan.
Tipranavir The serum concentration of Omaveloxolone can be increased when it is combined with Tipranavir.
Telithromycin The serum concentration of Omaveloxolone can be increased when it is combined with Telithromycin.
Ketoconazole The serum concentration of Omaveloxolone can be increased when it is combined with Ketoconazole.
Atazanavir The serum concentration of Omaveloxolone can be increased when it is combined with Atazanavir.
Amiodarone The serum concentration of Omaveloxolone can be increased when it is combined with Amiodarone.
Econazole The serum concentration of Omaveloxolone can be increased when it is combined with Econazole.
Nefazodone The serum concentration of Omaveloxolone can be increased when it is combined with Nefazodone.
Itraconazole The serum concentration of Omaveloxolone can be increased when it is combined with Itraconazole.
Clarithromycin The serum concentration of Omaveloxolone can be increased when it is combined with Clarithromycin.
Saquinavir The serum concentration of Omaveloxolone can be increased when it is combined with Saquinavir.
Posaconazole The serum concentration of Omaveloxolone can be increased when it is combined with Posaconazole.
Darunavir The serum concentration of Omaveloxolone can be increased when it is combined with Darunavir.
Danazol The serum concentration of Omaveloxolone can be increased when it is combined with Danazol.
Lopinavir The serum concentration of Omaveloxolone can be increased when it is combined with Lopinavir.
Ditiocarb The serum concentration of Omaveloxolone can be increased when it is combined with Ditiocarb.
Nilotinib The serum concentration of Omaveloxolone can be increased when it is combined with Nilotinib.
Telaprevir The serum concentration of Omaveloxolone can be increased when it is combined with Telaprevir.
Levoketoconazole The serum concentration of Omaveloxolone can be increased when it is combined with Levoketoconazole.
Lonafarnib The serum concentration of Omaveloxolone can be increased when it is combined with Lonafarnib.
Midostaurin The serum concentration of Omaveloxolone can be increased when it is combined with Midostaurin.
Boceprevir The serum concentration of Omaveloxolone can be increased when it is combined with Boceprevir.
Cobicistat The serum concentration of Cobicistat can be decreased when it is combined with Omaveloxolone.
Elvitegravir The serum concentration of Omaveloxolone can be increased when it is combined with Elvitegravir.
Stiripentol The serum concentration of Omaveloxolone can be increased when it is combined with Stiripentol.
Curcumin The serum concentration of Omaveloxolone can be increased when it is combined with Curcumin.
Ribociclib The serum concentration of Omaveloxolone can be increased when it is combined with Ribociclib.
Danoprevir The serum concentration of Omaveloxolone can be increased when it is combined with Danoprevir.
Troleandomycin The serum concentration of Omaveloxolone can be increased when it is combined with Troleandomycin.
Cyclosporine The serum concentration of Omaveloxolone can be increased when it is combined with Cyclosporine.
Fluvoxamine The serum concentration of Omaveloxolone can be increased when it is combined with Fluvoxamine.
Fluconazole The serum concentration of Omaveloxolone can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Omaveloxolone can be increased when it is combined with Erythromycin.
Lovastatin The serum concentration of Lovastatin can be decreased when it is combined with Omaveloxolone.
Ziprasidone The serum concentration of Omaveloxolone can be increased when it is combined with Ziprasidone.
Isradipine The serum concentration of Omaveloxolone can be increased when it is combined with Isradipine.
Diltiazem The serum concentration of Omaveloxolone can be increased when it is combined with Diltiazem.
Clozapine The serum concentration of Omaveloxolone can be increased when it is combined with Clozapine.
Haloperidol The serum concentration of Omaveloxolone can be increased when it is combined with Haloperidol.
Ciprofloxacin The serum concentration of Omaveloxolone can be increased when it is combined with Ciprofloxacin.
Nicardipine The serum concentration of Omaveloxolone can be increased when it is combined with Nicardipine.
Verapamil The serum concentration of Omaveloxolone can be increased when it is combined with Verapamil.
Aprepitant The serum concentration of Omaveloxolone can be increased when it is combined with Aprepitant.
Isoniazid The serum concentration of Omaveloxolone can be increased when it is combined with Isoniazid.
Tioconazole The serum concentration of Omaveloxolone can be increased when it is combined with Tioconazole.
Primaquine The serum concentration of Omaveloxolone can be increased when it is combined with Primaquine.
Miconazole The serum concentration of Omaveloxolone can be increased when it is combined with Miconazole.
Fusidic acid The serum concentration of Omaveloxolone can be increased when it is combined with Fusidic acid.
Zimelidine The serum concentration of Omaveloxolone can be increased when it is combined with Zimelidine.
Dronedarone The serum concentration of Omaveloxolone can be increased when it is combined with Dronedarone.
Milnacipran The serum concentration of Omaveloxolone can be increased when it is combined with Milnacipran.
Simeprevir The serum concentration of Omaveloxolone can be increased when it is combined with Simeprevir.
Isavuconazonium The serum concentration of Omaveloxolone can be increased when it is combined with Isavuconazonium.
Desvenlafaxine The serum concentration of Omaveloxolone can be increased when it is combined with Desvenlafaxine.
Nilvadipine The serum concentration of Omaveloxolone can be increased when it is combined with Nilvadipine.
Seproxetine The serum concentration of Omaveloxolone can be increased when it is combined with Seproxetine.
Crizotinib The serum concentration of Crizotinib can be decreased when it is combined with Omaveloxolone.
Linagliptin The serum concentration of Omaveloxolone can be increased when it is combined with Linagliptin.
Luliconazole The serum concentration of Omaveloxolone can be increased when it is combined with Luliconazole.
Indalpine The serum concentration of Omaveloxolone can be increased when it is combined with Indalpine.
Netupitant The serum concentration of Omaveloxolone can be increased when it is combined with Netupitant.
Barnidipine The serum concentration of Omaveloxolone can be increased when it is combined with Barnidipine.
Benidipine The serum concentration of Omaveloxolone can be increased when it is combined with Benidipine.
Venetoclax The serum concentration of Omaveloxolone can be increased when it is combined with Venetoclax.
Isavuconazole The serum concentration of Omaveloxolone can be increased when it is combined with Isavuconazole.
Fosnetupitant The serum concentration of Omaveloxolone can be increased when it is combined with Fosnetupitant.
Berotralstat The serum concentration of Omaveloxolone can be increased when it is combined with Berotralstat.
Phenytoin The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Phenytoin.
Pentobarbital The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Pentobarbital.
Carbamazepine The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Carbamazepine.
Mitotane The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Mitotane.
Primidone The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Primidone.
Rimexolone The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Rimexolone.
Rifampin The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Rifampicin.
Phenobarbital The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Phenobarbital.
Rifapentine The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Rifapentine.
Dexamethasone The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Dexamethasone.
Fosphenytoin The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Fosphenytoin.
St. John's Wort The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with St. John's Wort.
Enzalutamide The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Enzalutamide.
Lumacaftor The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Lumacaftor.
Apalutamide The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Apalutamide.
Bexarotene The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Bexarotene.
Bosentan The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Bosentan.
Nafcillin The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Nafcillin.
Modafinil The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Modafinil.
Etravirine The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Etravirine.
Avasimibe The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Avasimibe.
Echinacea The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Echinacea.
Dexamethasone acetate The therapeutic efficacy of Omaveloxolone can be decreased when used in combination with Dexamethasone acetate.

Target Protein

Nuclear factor erythroid 2-related factor 2 NFE2L2
Kelch-like ECH-associated protein 1 KEAP1

Referensi & Sumber

Synthesis reference: Sheikh, AY et al. (2018). Bardoxolonmethyl-2,2-difluoropropionamide derivatives, polymorphe forms and procedures for use thereof. DK/EP 2989114 T3. Danish Patent and Trademark Office. Available at https://patentimages.storage.googleapis.com/51/87/43/97d0fb3e69ee73/DK2989114T3.pdf
Artikel (PubMed)
  • PMID: 32909841
    Zesiewicz TA, Hancock J, Ghanekar SD, Kuo SH, Dohse CA, Vega J: Emerging therapies in Friedreich's Ataxia. Expert Rev Neurother. 2020 Dec;20(12):1215-1228. doi: 10.1080/14737175.2020.1821654. Epub 2020 Sep 21.
  • PMID: 36238561
    Jiang Z, Qi G, Lu W, Wang H, Li D, Chen W, Ding L, Yang X, Yuan H, Zeng Q: Omaveloxolone inhibits IL-1beta-induced chondrocyte apoptosis through the Nrf2/ARE and NF-kappaB signalling pathways in vitro and attenuates osteoarthritis in vivo. Front Pharmacol. 2022 Sep 27;13:952950. doi: 10.3389/fphar.2022.952950. eCollection 2022.
  • PMID: 29538645
    Shekh-Ahmad T, Eckel R, Dayalan Naidu S, Higgins M, Yamamoto M, Dinkova-Kostova AT, Kovac S, Abramov AY, Walker MC: KEAP1 inhibition is neuroprotective and suppresses the development of epilepsy. Brain. 2018 May 1;141(5):1390-1403. doi: 10.1093/brain/awy071.
  • PMID: 25897966
    Probst BL, Trevino I, McCauley L, Bumeister R, Dulubova I, Wigley WC, Ferguson DA: RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity. PLoS One. 2015 Apr 21;10(4):e0122942. doi: 10.1371/journal.pone.0122942. eCollection 2015.
  • PMID: 30656180
    Lynch DR, Farmer J, Hauser L, Blair IA, Wang QQ, Mesaros C, Snyder N, Boesch S, Chin M, Delatycki MB, Giunti P, Goldsberry A, Hoyle C, McBride MG, Nachbauer W, O'Grady M, Perlman S, Subramony SH, Wilmot GR, Zesiewicz T, Meyer C: Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Ann Clin Transl Neurol. 2018 Nov 10;6(1):15-26. doi: 10.1002/acn3.660. eCollection 2019 Jan.
  • PMID: 36032663
    Zighan M, Arkadir D, Douiev L, Keller G, Miller C, Saada A: Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects. Front Mol Biosci. 2022 Aug 12;9:890653. doi: 10.3389/fmolb.2022.890653. eCollection 2022.

Contoh Produk & Brand

Produk: 4 • International brands: 1
Produk
  • Skyclarys
    Capsule • 50 mg • Oral • EU • Approved
  • Skyclarys
    Capsule • 50 mg • Oral • EU • Approved
  • Skyclarys
    Capsule • 50 mg/1 • Oral • US • Approved
  • Skyclarys
    Capsule • 50 mg/1 • Oral • US • Approved
International Brands
  • Skyclarys — Reata Pharmaceuticals

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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