plantar erythrodysesthesia syndrome (PPES), non-cutaneous RAS mutation-positive malignancies, and QTc prolongation.

Refer to the encorafenib prescribing information for dose modifications for adverse reactions associatedwith encorafenib.

2.4 Dosage Modifications for Moderate or Severe Hepatic Impairment

For patients with moderate (total bilirubin greater than 1.5 and less than or equal to 3 × ULN and any AST)or severe (total bilirubin levels greater than 3 × ULN and any AST) hepatic impairment, the recommended

dosage is 30 mg orally taken twice daily [see Use in Specific Populations (8.6), Clinical Pharmacology(12.3)].

3 DOSAGE FORMS AND STRENGTHS

Tablets: 15 mg, yellow/dark yellow, unscored biconvex oval film-coated tablets debossed with a stylized“A” on one side and “15” on the other side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Cardiomyopathy

Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomaticdecreases in ejection fraction, has been reported in patients treated with MEKTOVI in combination with

encorafenib. In COLUMBUS, evidence of cardiomyopathy (decrease in LVEF below the institutional LLNwith an absolute decrease in LVEF ≥ 10% below baseline as detected by echocardiography or MUGA)

occurred in 7% of patients receiving MEKTOVI plus encorafenib. Grade 3 left ventricular dysfunctionoccurred in 1.6% of patients. The median time to first occurrence of left ventricular dysfunction (any grade)

in patients receiving MEKTOVI in combination with encorafenib was 3.6 months (range 0 to 21 months).

Cardiomyopathy resolved in 87% of patients receiving MEKTOVI plus encorafenib.

Assess ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, one month afterinitiating treatment, and then every 2 to 3 months during treatment. The safety of MEKTOVI in combination

with encorafenib has not been established in patients with a baseline ejection fraction that is either below50% or below the institutional lower limit of normal (LLN). Patients with cardiovascular risk factors should

be monitored closely when treated with MEKTOVI.

Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage andAdministration (2.3), Adverse Reactions (6.1)].

5.2 Venous Thromboembolism

In COLUMBUS, venous thromboembolism (VTE) occurred in 6% of patients receiving MEKTOVI incombination with encorafenib, including 3.1% of patients who developed pulmonary embolism. Withhold,

reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage andAdministration (2.3), Adverse Reactions (6.1)]. 

5.3 Ocular Toxicities

Serous Retinopathy

In COLUMBUS, serous retinopathy occurred in 20% of patients treated with MEKTOVI in combinationwith encorafenib; 8% were retinal detachment and 6% were macular edema. Symptomatic serous

retinopathy occurred in 8% of patients with no cases of blindness. No patient discontinued MEKTOVI dueto serous retinopathy; 6% of patients required dose interruptions or dose reductions. The median time to

onset of the first event of serous retinopathy (all grades) was 1.2 months (range 0 to 17.5 months).