COTELLIC is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. (1, 14)

Limitation of Use: COTELLIC is not indicated for treatment of patients with wild-type BRAF melanoma.

• Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of COTELLIC. (2.1)
• The recommended dose is 60 mg orally once daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Take COTELLIC with or without food. (2.2)

Tablets: 20 mg (3)
CONTRAINDICATIONS

None. (4)
WARNINGS AND PRECAUTIONS

• New primary malignancies, cutaneous and non-cutaneous: Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and for up to 6 months following the last dose of COTELLIC. (5.1)
• Hemorrhage: Major hemorrhagic events can occur with COTELLIC. Monitor for signs and symptoms of bleeding. (5.2, 2.4)
• Cardiomyopathy: The risk of cardiomyopathy is increased in patients receiving COTELLIC with vemurafenib compared with vemurafenib as a single agent. The safety of COTELLIC has not been established in patients with decreased left ventricular ejection fraction (LVEF). eva luate LVEF before treatment, after one month of treatment, then every 3 months thereafter during treatment with COTELLIC. (5.3, 2.4)
• Severe Dermatologic Reactions: Monitor for severe skin rashes. Interrupt, reduce, or discontinue COTELLIC. (5.4, 2.4)
• Serous Retinopathy and Retinal Vein Occlusion: Perform an ophthalmological eva luation at regular intervals and for any visual disturbances. Permanently discontinue COTELLIC for retinal vein occlusion (RVO). (5.5, 2.4)
• Hepatotoxicity: Monitor liver laboratory tests during treatment and as clinically indicated. (5.6, 2.4)
• Rhabdomyolysis: Monitor creatine phosphokinase periodically and as clinically indicated for signs and symptoms of rhabdomyolysis. (5.7, 2.4)
• Severe Photosensitivity: Advise patients to avoid sun exposure. (5.8, 2.4)
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.9, 8.1, 8.3)

Most common adverse reactions for COTELLIC (≥20%) are diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting. The most common (≥5%) Grade 3-4 laboratory abnormalities are increased GGT, increased CPK, hypophosphatemia, increased ALT, lymphopenia, increased AST, increased alkaline phosphatase, hyponatremia. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Avoid concomitant administration of COTELLIC with strong or moderate CYP3A inducers or inhibitors. (2.3, 7.1, 7.2)

Lactation: Do not breastfeed while taking COTELLIC. (8.2)