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INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE
COTELLIC (cobimetinib) is indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with ZELBORAF (vemurafenib).

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
Review the Full Prescribing Information for ZELBORAF for information on the serious risks of ZELBORAF.

The following can occur in patients treated with COTELLIC:

New primary malignancies, including cutaneous and non-cutaneous malignancies
Hemorrhage, including major hemorrhages
Cardiomyopathy, defined as symptomatic and asymptomatic decline in left ventricular ejection fraction
Severe dermatologic reactions, including rash and other skin reactions
Serous retinopathy and retinal vein occlusion
Hepatotoxicity
Rhabdomyolysis
Severe photosensitivity
Embryo-fetal toxicity

The following can occur in patients treated with ZELBORAF:

New primary malignancies including cutaneous squamous cell carcinoma, non-cutaneous squamous cell carcinoma, new primary melanoma, and other malignancies
Tumor promotion in BRAF wild-type melanomas
Serious hypersensitivity reactions including anaphylaxis
Severe dermatologic reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis
QT prolongation
Hepatotoxicity including liver injury leading to functional hepatic impairment (including coagulopathy or other organ dysfunction); increases in transaminases and bilirubin when concurrently administered with ipilimumab
Photosensitivity
Ophthalmologic reactions, including uveitis, blurry vision, and photophobia
Embryo-fetal toxicity
Radiation sensitization and radiation recall, including fatal cases in patients with visceral involvement
Renal failure, including acute interstitial nephritis and acute tubular necrosis
Dupuytren's contracture and plantar fascial fibromatosis

DRUG INTERACTIONS

Avoid concomitant administration of COTELLIC with strong or moderate CYP3A inducers or inhibitors.
Avoid concurrent use of ZELBORAF with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP1A2 and P-glycoprotein substrates with narrow therapeutic windows.

USE IN SPECIFIC POPULATIONS: Lactation
Advise women not to breastfeed during treatment with COTELLIC and ZELBORAF and for 2 weeks after the final dose of COTELLIC or ZELBORAF (whichever is taken later).

Most Common Adverse Reactions
The most common (≥20%) adverse reactions with COTELLIC were diarrhea (60%), photosensitivity reaction (46%), nausea (41%), pyrexia (28%), and vomiting (24%). The most common (≥5%) Grade 3-4 laboratory abnormalities were increased GGT (21%), increased CPK (14%), hypophosphatemia (12%), increased ALT (11%), lymphopenia (10%), increased AST (8%), increased alkaline phosphatase (7%), and hyponatremia (6%).

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see both Full COTELLIC Prescribing Information and Full ZELBORAF Prescribing Information for additional Important Safety Information.