new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold,reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage and

Administration (2.3), Adverse Reactions (6.1)].

Retinal Vein Occlusion

RVO is a known class-related adverse reaction of MEK inhibitors and may occur in patients treated withMEKTOVI in combination with encorafenib. In patients with BRAF mutation-positive melanoma receiving

MEKTOVI with encorafenib (n=690), 1 patient experienced RVO (0.1%).

The safety of MEKTOVI has not been established in patients with a history of RVO or current risk factorsfor RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes.

Perform ophthalmologic eva luation for patient-reported acute vision loss or other visual disturbance within24 hours. Permanently discontinue MEKTOVI in patients with documented RVO [see Dosage and

Administration (2.3), Adverse Reactions (6.1)].

Uveitis

Uveitis, including iritis and iridocyclitis, has been reported in patients treated with MEKTOVI incombination with encorafenib. In COLUMBUS, the incidence of uveitis among patients treated with

MEKTOVI in combination with encorafenib was 4%.

Assess for visual symptoms at each visit. Perform an ophthalmologic eva luation at regular intervals and fornew or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold,

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

5.4 Interstitial Lung Disease

In patients with BRAF mutation-positive melanoma receiving MEKTOVI with encorafenib (n=690),2 patients (0.3%) developed interstitial lung disease (ILD), including pneumonitis.

Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. Withhold, reducedose, or permanently discontinue based on severity of adverse reaction [see Dosage and Administration

(2.3), Adverse Reactions (6.1)].

5.5 Hepatotoxicity

Hepatotoxicity can occur when MEKTOVI is administered in combination with encorafenib. 

InCOLUMBUS, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receivingMEKTOVI in combination with encorafenib was 6% for alanine aminotransferase (ALT), 2.6% for aspartate

aminotransferase (AST), and 0.5% for alkaline phosphatase. No patient experienced Grade 3 or 4 serumbilirubin elevation.

Monitor liver laboratory tests before initiation of MEKTOVI, monthly during treatment, and as clinicallyindicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction [see

Dosage and Administration (2.3), Adverse Reactions (6.1)]. 

5.6 Rhabdomyolysis

Rhabdomyolysis can occur when MEKTOVI is administered in combination with encorafenib. 

InCOLUMBUS, elevation of laboratory values of serum CPK occurred in 58% of patients treated with MEKTOVI in combination with encorafenib. In patients with BRAF mutation-positive melanoma receiving

MEKTOVI with encorafenib (n=690), rhabdomyolysis was reported in 1 patient (0.1%).