Binimetinib (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- BINIMETINIB
- MEKTOVI
Contraindications
None.
Adverse Reactions
The following adverse reactions are described elsewhere in the labeling: •New Primary Malignancies [see Warnings and Precautions (5.1)] •Cardiomyopathy [see Warnings and Precautions (5.2) ] •Venous Thromboembolism [see Warnings and Precautions (5.3) ] •Ocular Toxicities [see Warnings and Precautions (5.4) ] •Interstitial Lung Disease [see Warnings and Precautions (5.5) ] •Hepatotoxicity [see Warnings and Precautions (5.6) ] •Rhabdomyolysis [see Warnings and Precautions (5.7) ] •Hemorrhage [see Warnings and Precautions (5.8) ] •Embryo-Fetal Toxicity [see Warnings and Precautions (5.9)] •Risks Associated with Combination Treatment [see Warnings and Precautions (5.10)]
Drug Interactions
No clinically important drug interactions have been observed with MEKTOVI.
Mechanism of Action
Binimetinib is a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. In vitro, binimetinib inhibited extracellular signal-related kinase (ERK) phosphorylation in cell-free assays as well as viability and MEK-dependent phosphorylation of BRAF-mutant human melanoma cell lines. Binimetinib also inhibited in vivo ERK phosphorylation and tumor growth in BRAF-mutant murine xenograft models. Binimetinib and encorafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared to either drug alone, coadministration of encorafenib and binimetinib resulted in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. Additionally, the combination of binimetinib and encorafenib delayed the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared to either drug alone. In a BRAF V600E mutant NSCLC patient-derived xenograft model in mice, coadministration of encorafenib and binimetinib resulted in greater anti-tumor activity compared to binimetinib alone, with respect to tumor growth inhibition. Increased tumor growth delay after dosing cessation was also observed with the coadministration compared to either drug alone.
Overdosage
Since binimetinib is 97% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with MEKTOVI.