BRAFTOVI dose prior to concurrent use of moderate CYP3A4 inhibitors. After the inhibitor has beendiscontinued for 3 to 5 elimination half-lives, resume the BRAFTOVI dose that was taken prior to initiating

the CYP3A4 inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Capsules, hard gelatin:

 50 mg: stylized “A” on orange cap and “LGX 50mg” on beige body

 75 mg: stylized “A” on beige cap and “LGX 75mg” on white body

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 New Primary Malignancies

New primary malignancies, cutaneous and non-cutaneous, have been observed in patients treated withBRAF inhibitors and can occur with BRAFTOVI.

Cutaneous Malignancies

In COLUMBUS, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurredin 2.6%, and basal cell carcinoma occurred in 1.6% of patients who received BRAFTOVI in combination

with binimetinib. Median time to first occurrence of cuSCC/KA was 5.8 months (range 1 to 9 months)[see Adverse Reactions (6.1)].

For patients who received BRAFTOVI as a single agent, cuSCC/KA was reported in 8%, basal cellcarcinoma in 1%, and a new primary melanoma in 5% of patients.

Perform dermatologic eva luations prior to initiating treatment, every 2 months during treatment, and for upto 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and

dermatopathologic eva luation. Dose modification is not recommended for new primary cutaneousmalignancies.

Non-Cutaneous Malignancies

Based on its mechanism of action, BRAFTOVI may promote malignancies associated with activation ofRAS through mutation or other mechanisms [see Warnings and Precautions (5.2)].

Monitor patientsreceiving BRAFTOVI for signs and symptoms of non-cutaneous malignancies. Discontinue BRAFTOVI forRAS mutation-positive non-cutaneous malignancies [see Dosage and Administration (2.3)].

5.2 Tumor Promotion in BRAF Wild-Type Tumors

In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cellproliferation in BRAF wild-type cells, which are exposed to BRAF inhibitors. Confirm evidence of BRAF

V600E or V600K mutation prior to initiating BRAFTOVI [see Indications and Usage (1), Dosage andAdministration (2.1)].

5.3 Hemorrhage

Hemorrhage can occur when BRAFTOVI is administered in combination with binimetinib. In COLUMBUS,hemorrhage occurred in 19% of patients receiving BRAFTOVI in combination with binimetinib; Grade 3 or

greater hemorrhage occurred in 3.2% of patients. The most frequent hemorrhagic events weregastrointestinal, including rectal hemorrhage (4.2%), hematochezia (3.1%), and hemorrhoidal hemorrhage

(1%). Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6%of patients. 

 

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

5.4 Uveitis