Binimetinib

Uses

Binimetinib is a medication used to treat metastatic melanoma with specific mutations.

On June 27, 2018, the Food and Drug Administration approved encorafenib and binimetinib in combination patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test .

Binimetinib is also used to associated treatment for these conditions: Metastatic Melanoma, Unresectable Melanoma

How Binimetinib works

Binimetinib, noncompetitive with ATP, binds to and inhibits the activity of MEK1/2. The inhibition of MEK1/2 prevents the activation of MEK1/2-dependent effector proteins and transcription factors. This process can result in the inhibition of growth factor-mediated cell signaling. This may lead to the inhibition of tumor cell proliferation and an inhibition in the production of various inflammatory cytokines including interleukin-1, -6 and tumor necrosis factor. MEK1/2 are themselves threonine and tyrosine kinases that possess a dual specificity. They subsequently contribute critically to the activation of the RAS/RAF/MEK/ERK pathway and are typically upregulated in a number of different tumor cell types .

Toxicity

The most common (≥25%) adverse reactions in patients receiving the combination of this drug with Encorafenib were fatigue, nausea, diarrhea, vomiting, abdominal pain, and arthralgia. Discontinuation of therapy due to adverse reactions occurred in 5% of patients receiving the combination; the most common reasons were hemorrhage and headache .

Due to the variety of adverse events associated with this drug, adverse events are categorized by system :

Systemic events: Fatigue (31%)

Musculoskeletal system: Rhabdomyolysis

Ophthalmic events: Retinal hemorrhage, retinal detachment (6%), macular edema, serous retinopathy (20%)

Circulatory system: Hypertension, thromboembolic events such as DVT, resulting in pulmonary embolism (5.6%), peripheral edema or periorbital edema (43.5%), hemorrhage (11.2%)

Pulmonary events: Pneumonitis (1.9%), Pulmonary embolism

Cardiovascular system: QT interval prolongation (3.3%), Left ventricular dysfunction (7%)

Gastrointestinal system: Hepatotoxicity, diarrhea, nausea, vomiting, stomatitis, dry mouth

Dermatologic events: Acneiform dermatitis

Based on findings from animal studies and its mechanism of action, MEKTOVI can cause fetal harm when administered to a pregnant woman .

Food Interaction

• Take with or without food.

Binimetinib Drug Interaction

Moderate: valproic acidUnknown: paclitaxel protein-bound, charcoal, doxorubicin, bevacizumab, betamethasone topical, bictegravir / emtricitabine / tenofovir alafenamide, multivitamin with minerals, tadalafil, arginine, levocarnitine, cysteine, lithium, acetaminophen, thiamine, cyanocobalamin, pyridoxine, cholecalciferol, phytonadione, menaquinone

Binimetinib Disease Interaction

Moderate: cardiomyopathy, hepatic impairment, retinal disturbances

Volume of Distribution

The geometric mean (CV%) of apparent volume of distribution of binimetinib is 92 L (45%)

Elimination Route

Following oral administration in a pharmacokinetic study, at least 50% of the binimetinib dose was absorbed with a median time to maximum concentration (Tmax) of 1.6 hours .

The administration of a single dose of MEKTOVI 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 .

Half Life

The mean (CV%) terminal half-life (t1/2) of binimetinib is 3.5 hours (28.5%) .

Clearance

20.2 L/h (24%)

Elimination Route

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 .

Innovators Monograph

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