BRAFTOVI in combination with binimetinib 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)].

5.5 QT Prolongation

BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients [see ClinicalPharmacology (12.2)]. In COLUMBUS, an increase in QTcF to > 500 ms was measured in 0.5% (1/192) of

patients who received BRAFTOVI in combination with binimetinib.

Monitor patients who already have or who are at significant risk of developing QTc prolongation, includingpatients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled

heart failure and those taking other medicinal products associated with QT prolongation. Correcthypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose,

or permanently discontinue for QTc > 500 ms [see Dosage and Administration (2.3), Adverse Reactions(6.1)].

5.6 Embryo-Fetal Toxicity

Based on its mechanism of action, BRAFTOVI can cause fetal harm when administered to a pregnantwoman. Encorafenib produced embryo-fetal developmental changes in rats and rabbits and was an

abortifacient in rabbits at doses greater than or equal to those resulting in exposures approximately 26 (in therat) and 178 (in the rabbit) times the human exposure at the recommended dose of 450 mg, with no clear

findings at lower doses.

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective,non-hormonal method of contraception since BRAFTOVI can render hormonal contraceptives ineffective,

during treatment and for 2 weeks after the final dose of BRAFTOVI [see Use in Specific Populations (8.1,8.3)].

5.7 Risks Associated with BRAFTOVI as a Single Agent

BRAFTOVI when used as a single agent is associated with an increased risk of certain adverse reactionscompared to when BRAFTOVI is used in combination with binimetinib. Grades 3 or 4 dermatologic

reactions occurred in 21% of patients treated with BRAFTOVI single agent compared to 2% of patientstreated with BRAFTOVI in combination with binimetinib [see Warnings and Precautions (5.1), Adverse

Reactions (6.1)].

If binimetinib is temporarily interrupted or permanently discontinued, reduce the dose of BRAFTOVI asrecommended [see Dosage and Administration (2.3)].

5.8 Risks Associated with Combination Treatment

BRAFTOVI is indicated for use in combination with binimetinib. Refer to the binimetinib prescribinginformation for additional risk information that applies to combination use treatment.

6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

 New Primary Malignancies [see Warnings and Precautions (5.1)]

 

 Hemorrhage [see Warnings and Precautions (5.3)]

 

 Uveitis [see Warnings and Precautions (5.4)]

 

 QT Prolongation [see Warnings and Precautions (5.5)]