Peringatan Keamanan

Based on findings from animal reproduction studies and its mechanism of action, binimetinib can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of binimetinib during pregnancy. In animal reproduction studies, oral administration of binimetinib during the period of organogenesis was embryotoxic and an abortifacient in rabbits at doses greater than or equal to those resulting in exposures approximately 5 times the human exposure at the clinical dose of 45 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.L48606

No overall differences in the safety or effectiveness of MEKTOVI plus encorafenib were observed in older patients as compared to younger patients.L48606

Since binimetinib is 97% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with binimetinib.L48606

Carcinogenicity studies with binimetinib have not been conducted. Binimetinib was not genotoxic in studies evaluating reverse mutations in bacteria, chromosomal aberrations in mammalian cells, or micronuclei in the bone marrow of rats.L48606

Binimetinib

DB11967

small molecule approved investigational

Deskripsi

Binimetinib, also known as Mektovi, is a potent and selective oral mitogen-activated protein kinase 1/2 (MEK 1/2) inhibitor which is combined with Encorafenib.A34275,L3335

On June 27, 2018, the Food and Drug Administration approved the combination of Encorafenib and binimetinib (BRAFTOVI and MEKTOVI, from Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with the BRAF V600E or V600K mutations, as detected by an FDA-approved test.L3335

Struktur Molekul 2D

Berat 441.233
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean (CV%) terminal half-life (t1/2) of binimetinib is 3.5 hours (28.5%).[L48606]
Volume Distribusi The geometric mean (CV%) of the apparent volume of distribution of binimetinib is 92 L (45%).[L48606]
Klirens (Clearance) The apparent clearance (CL/F) of binimetinib is is 20.2 L/h (24%).[L48606]

Absorpsi

The pharmacokinetics of binimetinib was studied in healthy subjects and patients with solid tumors. After twice-daily dosing, the accumulation is 1.5-fold and the coefficient of variation (CV%) of the area under the concentration-time curve (AUC) is <40% at steady state. The systemic exposure of binimetinib is approximately dose proportional.L48606 After oral administration, at least 50% of the binimetinib dose was absorbed with a median time to maximum concentration (Tmax) of 1.6 hours.L48606 The administration of a single dose of binimetinib 45 mg with a high-fat, high-calorie meal (consisting of approximately 150 calories from protein, 350 calories from carbohydrate, and 500 calories from fat) in healthy subjects had no effect on binimetinib exposure.L48606

Metabolisme

The primary metabolic pathway is glucuronidation with UGT1A1 contributing up to 61% of the binimetinib metabolism. Other pathways of binimetinib metabolism include N-dealkylation, amide hydrolysis, and loss of ethane-diol from the side chain. The active metabolite M3 produced by CYP1A2 and CYP2C19 represents 8.6% of the binimetinib exposure. Following a single oral dose of 45 mg radiolabeled binimetinib, approximately 60% of the circulating radioactivity AUC in plasma was attributable to binimetinib.L48606

Rute Eliminasi

Following a single oral dose of 45 mg radiolabeled binimetinib in healthy subjects, 62% (32% unchanged) of the administered dose was recovered in the feces while 31% (6.5% unchanged) was recovered in the urine.L48606

Interaksi Makanan

1 Data
  • 1. Take with or without food.

Interaksi Obat

659 Data
Deferasirox The serum concentration of Binimetinib can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Binimetinib can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Binimetinib can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Binimetinib can be decreased when it is combined with Teriflunomide.
Abiraterone The serum concentration of Binimetinib can be increased when it is combined with Abiraterone.
Cyproterone acetate The metabolism of Binimetinib can be increased when combined with Cyproterone acetate.
Albendazole The metabolism of Binimetinib can be increased when combined with Albendazole.
Caffeine The metabolism of Binimetinib can be decreased when combined with Caffeine.
Moxifloxacin The metabolism of Binimetinib can be decreased when combined with Moxifloxacin.
Lidocaine The risk or severity of methemoglobinemia can be increased when Binimetinib is combined with Lidocaine.
Mexiletine The metabolism of Binimetinib can be decreased when combined with Mexiletine.
Imipramine The metabolism of Binimetinib can be decreased when combined with Imipramine.
Alosetron The metabolism of Binimetinib can be decreased when combined with Alosetron.
Gatifloxacin The metabolism of Binimetinib can be decreased when combined with Gatifloxacin.
Dosulepin The metabolism of Binimetinib can be decreased when combined with Dosulepin.
Lobeglitazone The metabolism of Binimetinib can be decreased when combined with Lobeglitazone.
Pazufloxacin The metabolism of Binimetinib can be decreased when combined with Pazufloxacin.
Osilodrostat The serum concentration of Binimetinib can be increased when it is combined with Osilodrostat.
Osimertinib The serum concentration of Binimetinib can be decreased when it is combined with Osimertinib.
Vemurafenib The serum concentration of Binimetinib can be increased when it is combined with Vemurafenib.
Rifampin The serum concentration of Binimetinib can be decreased when it is combined with Rifampicin.
Levothyroxine The serum concentration of Binimetinib can be decreased when it is combined with Levothyroxine.
Trazodone The serum concentration of Binimetinib can be decreased when it is combined with Trazodone.
St. John's Wort The serum concentration of Binimetinib can be decreased when it is combined with St. John's Wort.
Apalutamide The serum concentration of Binimetinib can be decreased when it is combined with Apalutamide.
Prednisolone phosphate The serum concentration of Binimetinib can be decreased when it is combined with Prednisolone phosphate.
Dexamethasone acetate The serum concentration of Binimetinib can be decreased when it is combined with Dexamethasone acetate.
Ritonavir The serum concentration of Binimetinib can be increased when it is combined with Ritonavir.
Tipranavir The serum concentration of Binimetinib can be decreased when it is combined with Tipranavir.
Sorafenib The serum concentration of Binimetinib can be increased when it is combined with Sorafenib.
Ketoconazole The serum concentration of Binimetinib can be increased when it is combined with Ketoconazole.
Nilotinib The serum concentration of Binimetinib can be increased when it is combined with Nilotinib.
Regorafenib The serum concentration of Binimetinib can be increased when it is combined with Regorafenib.
Dacomitinib The serum concentration of Binimetinib can be increased when it is combined with Dacomitinib.
Rucaparib The metabolism of Binimetinib can be decreased when combined with Rucaparib.
Enasidenib The serum concentration of Binimetinib can be increased when it is combined with Enasidenib.
Pibrentasvir The serum concentration of Binimetinib can be increased when it is combined with Pibrentasvir.
Glecaprevir The serum concentration of Binimetinib can be increased when it is combined with Glecaprevir.
Simeprevir The serum concentration of Binimetinib can be increased when it is combined with Simeprevir.
Amiodarone The serum concentration of Binimetinib can be increased when it is combined with Amiodarone.
Propafenone The serum concentration of Binimetinib can be increased when it is combined with Propafenone.
Mibefradil The serum concentration of Binimetinib can be increased when it is combined with Mibefradil.
Verapamil The serum concentration of Binimetinib can be increased when it is combined with Verapamil.
Carvedilol The serum concentration of Binimetinib can be increased when it is combined with Carvedilol.
Voxilaprevir The serum concentration of Binimetinib can be increased when it is combined with Voxilaprevir.
Quinidine The serum concentration of Binimetinib can be increased when it is combined with Quinidine.
Tamoxifen The serum concentration of Binimetinib can be increased when it is combined with Tamoxifen.
Quinine The serum concentration of Binimetinib can be increased when it is combined with Quinine.
Istradefylline The serum concentration of Binimetinib can be increased when it is combined with Istradefylline.
Methylene blue The serum concentration of Binimetinib can be increased when it is combined with Methylene blue.
Cyclosporine The serum concentration of Binimetinib can be increased when it is combined with Cyclosporine.
Fluconazole The serum concentration of Binimetinib can be increased when it is combined with Fluconazole.
Erythromycin The serum concentration of Binimetinib can be increased when it is combined with Erythromycin.
Sildenafil The serum concentration of Binimetinib can be increased when it is combined with Sildenafil.
Reserpine The serum concentration of Binimetinib can be increased when it is combined with Reserpine.
Ranolazine The serum concentration of Binimetinib can be increased when it is combined with Ranolazine.
Loxapine The serum concentration of Binimetinib can be increased when it is combined with Loxapine.
Toremifene The serum concentration of Binimetinib can be increased when it is combined with Toremifene.
Simvastatin The serum concentration of Binimetinib can be increased when it is combined with Simvastatin.
Mifepristone The serum concentration of Binimetinib can be decreased when it is combined with Mifepristone.
Vardenafil The serum concentration of Binimetinib can be increased when it is combined with Vardenafil.
Tacrolimus The serum concentration of Binimetinib can be increased when it is combined with Tacrolimus.
Conivaptan The serum concentration of Binimetinib can be increased when it is combined with Conivaptan.
Zonisamide The serum concentration of Binimetinib can be increased when it is combined with Zonisamide.
Norgestimate The serum concentration of Binimetinib can be increased when it is combined with Norgestimate.
Itraconazole The serum concentration of Binimetinib can be increased when it is combined with Itraconazole.
Clarithromycin The serum concentration of Binimetinib can be increased when it is combined with Clarithromycin.
Saquinavir The serum concentration of Binimetinib can be increased when it is combined with Saquinavir.
Lapatinib The serum concentration of Binimetinib can be increased when it is combined with Lapatinib.
Paliperidone The serum concentration of Binimetinib can be increased when it is combined with Paliperidone.
Lopinavir The serum concentration of Binimetinib can be increased when it is combined with Lopinavir.
Biricodar The serum concentration of Binimetinib can be increased when it is combined with Biricodar.
Dronedarone The serum concentration of Binimetinib can be increased when it is combined with Dronedarone.
Elacridar The serum concentration of Binimetinib can be increased when it is combined with Elacridar.
Flibanserin The serum concentration of Binimetinib can be increased when it is combined with Flibanserin.
Vandetanib The serum concentration of Binimetinib can be increased when it is combined with Vandetanib.
Telaprevir The serum concentration of Binimetinib can be increased when it is combined with Telaprevir.
Zosuquidar The serum concentration of Binimetinib can be increased when it is combined with Zosuquidar.
Tariquidar The serum concentration of Binimetinib can be increased when it is combined with Tariquidar.
Temsirolimus The serum concentration of Binimetinib can be increased when it is combined with Temsirolimus.
Isavuconazonium The serum concentration of Binimetinib can be increased when it is combined with Isavuconazonium.
Brefeldin A The serum concentration of Binimetinib can be increased when it is combined with Brefeldin A.
Ticagrelor The serum concentration of Binimetinib can be increased when it is combined with Ticagrelor.
Ivacaftor The serum concentration of Binimetinib can be increased when it is combined with Ivacaftor.
Lomitapide The serum concentration of Binimetinib can be increased when it is combined with Lomitapide.
Crizotinib The serum concentration of Binimetinib can be increased when it is combined with Crizotinib.
Linagliptin The serum concentration of Binimetinib can be increased when it is combined with Linagliptin.
Carfilzomib The serum concentration of Binimetinib can be increased when it is combined with Carfilzomib.
Mirabegron The serum concentration of Binimetinib can be increased when it is combined with Mirabegron.
Ponatinib The serum concentration of Binimetinib can be increased when it is combined with Ponatinib.
Canagliflozin The serum concentration of Binimetinib can be increased when it is combined with Canagliflozin.
Afatinib The serum concentration of Binimetinib can be increased when it is combined with Afatinib.
Ledipasvir The serum concentration of Binimetinib can be increased when it is combined with Ledipasvir.
Vorapaxar The serum concentration of Binimetinib can be increased when it is combined with Vorapaxar.
Suvorexant The serum concentration of Binimetinib can be increased when it is combined with Suvorexant.
Netupitant The serum concentration of Binimetinib can be increased when it is combined with Netupitant.
Cobicistat The serum concentration of Binimetinib can be increased when it is combined with Cobicistat.
Palbociclib The serum concentration of Binimetinib can be increased when it is combined with Palbociclib.
Daclatasvir The serum concentration of Binimetinib can be increased when it is combined with Daclatasvir.
Niguldipine The serum concentration of Binimetinib can be increased when it is combined with Niguldipine.

Target Protein

Dual specificity mitogen-activated protein kinase kinase 2 MAP2K2
Dual specificity mitogen-activated protein kinase kinase 1 MAP2K1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 28587477
    Koelblinger P, Dornbierer J, Dummer R: A review of binimetinib for the treatment of mutant cutaneous melanoma. Future Oncol. 2017 Aug;13(20):1755-1766. doi: 10.2217/fon-2017-0170. Epub 2017 Jun 7.
  • PMID: 28152546
    Bendell JC, Javle M, Bekaii-Saab TS, Finn RS, Wainberg ZA, Laheru DA, Weekes CD, Tan BR, Khan GN, Zalupski MM, Infante JR, Jones S, Papadopoulos KP, Tolcher AW, Chavira RE, Christy-Bittel JL, Barrett E, Patnaik A: A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017 Feb 28;116(5):575-583. doi: 10.1038/bjc.2017.10. Epub 2017 Feb 2.

Contoh Produk & Brand

Produk: 6 • International brands: 0
Produk
  • Mektovi
    Tablet • 15 mg • Oral • Canada • Approved
  • Mektovi
    Tablet, film coated • 45 mg • Oral • EU • Approved
  • Mektovi
    Tablet, film coated • 45 mg • Oral • EU • Approved
  • Mektovi
    Tablet, film coated • 15 mg/1 • Oral • US • Approved
  • Mektovi
    Tablet, film coated • 15 mg • Oral • EU • Approved
  • Mektovi
    Tablet, film coated • 15 mg • Oral • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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