MEKINIST is a kinase inhibitor indicated, as a single agent or in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. (1, 14.1)

Limitation of use: MEKINIST is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy. (1)
DOSAGE AND ADMINISTRATION

• Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with MEKINIST. (2.1)
• The recommended dosage regimen of MEKINIST is 2 mg orally once daily. Take MEKINIST at least 1 hour before or at least 2 hours after a meal. (2.2)

Tablets: 0.5 mg and 2 mg. (3)
CONTRAINDICATIONS

None. (4)
WARNINGS AND PRECAUTIONS

• New primary malignancies, cutaneous and non-cutaneous, can occur when MEKINIST is used with dabrafenib. Monitor patients for new malignancies prior to initiation of therapy while on therapy, and following discontinuation of treatment. (5.1, 2.3)
• Hemorrhage: Major hemorrhagic events can occur. Monitor for signs and symptoms of bleeding (5.2, 2.3)
• Venous thromboembolism: Deep vein thrombosis and pulmonary embolism can occur in patients receiving MEKINIST. (5.3, 2.3).
• Cardiomyopathy: Assess LVEF before treatment, after one month of treatment, then every 2 to 3 months thereafter. (5.4, 2.3)
• Ocular toxicities: Perform ophthalmologic eva luation for any visual disturbances. For Retinal Vein Occlusion (RVO), permanently discontinue MEKINIST. (5.5, 2.3).
• Interstitial lung disease (ILD): Withhold MEKINIST for new or progressive unexplained pulmonary symptoms. Permanently discontinue MEKINIST for treatment-related ILD or pneumonitis. (5.6, 2.3)
• Serious febrile reactions: Can occur when MEKINIST is used with dabrafenib. (5.7, 2.3)
• Serious skin toxicity: Monitor for skin toxicities and for secondary infections. Discontinue MEKINIST for intolerable Grade 2, or Grade 3 or 4 rash not improving within 3 weeks despite interruption of MEKINIST. (5.8, 2.3)
• Hyperglycemia: Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia. (5.9, 2.3)
• Embryo-fetal toxicity: MEKINIST can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. (5.10, 8.1, 8.3)

• Most common adverse reactions (≥20%) for MEKINIST as a single agent include rash, diarrhea, and lymphedema. (6.1)
• Most common adverse reactions (≥20%) for MEKINIST with dabrafenib include pyrexia, nausea, rash, chills, diarrhea, vomiting, hypertension, and peripheral edema. (6.1)

  
  To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Lactation: Do not breast feed. (8.2)
• Females and Males of Reproductive Potential: May impair fertility. Counsel patients on pregnancy planning and prevention. (8.3)