Binimetinib Disease Interactions

Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients treated with binimetinib in combination with encorafenib. The median time to first occurrence of left ventricular dysfunction (any grade) in patients receiving treatment was 3.6 months (range 0 to 21 months). Cardiomyopathy resolved in 87% of the patients. Ejection fraction should be assessed by echocardiogram or MUGA scan prior to initiating treatment, one month after initiating treatment, and then every 2 to 3 months during treatment. The safety of this therapy has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal (LLN). Patients with cardiovascular risk factors should be monitored closely when treated with binimetinib.

Binimetinib concentrations may increase in patients with moderate or severe hepatic impairment. Reduce the dose of binimetinib for patients with moderate (total bilirubin > 1.5 and = 3 × ULN and any AST) or severe (total bilirubin levels > 3 × ULN and any AST) hepatic impairment. Dose adjustment is not recommended in patients with mild hepatic impairment (total bilirubin > 1 and = 1.5 × ULN and any AST or total bilirubin = ULN and AST > ULN).

Retinal vein occlusion (RVO) is a known class- related adverse reaction of MEK inhibitors and may occur in patients treated with binimetinib in combination with encorafenib. The safety of binimetinib has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. An ophthalmologic evaluation should be performed for patient reporting acute vision loss or other visual disturbance within 24 hours. Treatment should be discontinued in patients with documented RVO.