5.1 New Primary Malignancies

5.2 Tumor Promotion in BRAF Wild-Type Tumors

5.3 Hemorrhage

5.4 Uveitis

5.5 QT Prolongation

5.6 Embryo-Fetal Toxicity

5.7 Risks Associated with BRAFTOVI as a Single Agent

5.8 Risks Associated with Combination Treatment

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

7 DRUG INTERACTIONS

7.1 Effect of Other Drugs on BRAFTOVI

7.2 Effect of BRAFTOVI on Other Drugs

7.3 Drugs That Prolong the QT Interval

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are

not listed. 

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

BRAFTOVI™ is indicated, in combination with binimetinib, for the treatment of patients with unresectableor metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test

[see Dosage and Administration (2.1)].

Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma[see Warnings and Precautions (5.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Confirm the presence of a BRAF V600E or V600K mutation in tumor specimens prior to initiatingBRAFTOVI [see Warnings and Precautions (5.2), Clinical Studies (14)]. 

Information on FDA-approvedtests for the detection of BRAF V600E and V600K mutations in melanoma is available at:http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage

The recommended dosage of BRAFTOVI is 450 mg orally taken once daily in combination with binimetinibuntil disease progression or unacceptable toxicity. Refer to the binimetinib prescribing information for

recommended binimetinib dosing information.

BRAFTOVI may be taken with or without food [see Clinical Pharmacology (12.3)]. 

Do not take a misseddose of BRAFTOVI within 12 hours of the next dose of BRAFTOVI.

Do not take an additional dose if vomiting occurs after BRAFTOVI administration but continue with thenext scheduled dose.

2.3 Dosage Modifications for Adverse Reactions

If binimetinib is withheld, reduce BRAFTOVI to a maximum dose of 300 mg once daily until binimetinib isresumed [see Warnings and Precautions (5.7)].

Dose reductions for adverse reactions associated with BRAFTOVI are presented in Table 1.

Table 1: Recommended Dose Reductions for BRAFTOVI for Adverse Reactions

Action Recommended Dose

First Dose Reduction 300 mg orally once daily

Second Dose Reduction 200 mg orally once daily

Subsequent Modification Permanently discontinue if unable to tolerate BRAFTOVI 200 mg oncedailyDosage modifications for adverse reactions associated with BRAFTOVI are presented in Table 2.