• Monitor cardiac function (LVEF) by ECG or multigated acquisition (MUGA) scan before starting therapy with binimetinib, one mo after initiation of therapy, and then at 2- to 3-mo intervals during therapy. If asymptomatic, absolute decrease in LVEF >10% from baseline that is also below lower limit of normal (LLN) occurs, hold binimetinib for up to 4 wk and evaluate LVEF every 2 wk. Resume binimetinib at reduced dose if present: LVEF ≥ LLN and absolute decrease from baseline is ≤10% and patient is asymptomatic. If LVEF does not recover within 4 wk, permanently discontinue binimetinib. If symptomatic HF occurs with absolute decrease in LVEF >20% from baseline that is also below LLN, discontinue binimetinib permanently.
• Monitor for signs and symptoms of venous thromboembolism (shortness of breath, chest pain, arm or leg swelling, cool or pale arm or leg) during therapy. If uncomplicated DVT or PE occurs, hold binimetinib. If improves to Grade 0-1, resume at reduced dose. If not improved, permanently discontinue. If life-threatening PE occurs, permanently discontinue binimetinib.
• Assess for visual symptoms at each visit. Perform regular ophthalmologic exams. Monitor for signs and symptoms of ocular toxicities (blurred vision, loss of vision, other vision changes, see color dots, halo around objects), swelling, redness, photophobia, eye pain). If symptomatic retinopathy/retinal pigment epithelial detachments occur, hold binimetinib for up to 10 days. If improves and becomes asymptomatic, resume at same dose. If not improved, resume at a lower dose or permanently discontinue. If any grade RVO occurs, permanently discontinue binimetinib. If Grade 1–3 uveitis occurs, if Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, withhold binimetinib for up to 6 wk. If improved, resume at same or reduced dose. If not improved, permanently discontinue binimetinib. If Grade 4 uveitis occurs, permanently discontinue therapy.
• Monitor for signs and symptoms of ILD or pneumonitis (cough, dyspnea, hypoxia, pleural effusion, infiltrates) during therapy. If Grade 2 occurs, hold binimetinib for up to 4 wk. If improved to Grade 0–1, resume at reduced dose. If not resolved within 4 wk, permanently discontinue binimetinib. If Grade 3 or 4 occurs, discontinue binimetinib permanently.
• Assess for bleeding (headaches, dizziness, feeling weak, coughing up blood or blood clots, vomiting blood or vomit looks like "coffee grounds", red or black stools that look like tar) during therapy. If recurrent Grade 2 or first occurrence of Grade 3 occurs, hold binimetinib for up to 4 wk. If improves to Grade 0–1 or to pretreatment/baseline levels, resume at reduced dose. If no improvement, permanently discontinue binimetinib. If first occurrence of Grade 4 hemorrhagic event occurs, permanently discontinue binimetinib, or hold for up to 4 wk. If improves to Grade 0–1 or to pretreatment/baseline levels, resume at reduced dose. If no improvement, permanently discontinue. If recurrent Grade 3 hemorrhagic event occurs, consider discontinuing binimetinib permanently. If recurrent Grade 4 hemorrhagic event occurs, permanently discontinue therapy.

Lab Test Considerations:

• Verify negative pregnancy test prior to starting therapy.
  • Confirm presence of BRAF V600E or V600K mutation in tumor specimens before starting therapy. Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.
  • Monitor liver function tests before starting therapy, monthly during therapy, and as indicated. If Grade 2 AST or ALT increased, continue dose. If no improvement within 2 wk, hold binimetinib until improved to Grade 0–1 or to pretreatment/baseline levels and resume at same dose. If Grade 3 or 4 AST or increased ALT occurs, consider permanently discontinuing binimetinib.
  • May cause rhabdomyolysis. Monitor CK and serum creatinine levels prior to starting therapy, periodically during therapy, and as indicated. If Grade 4 asymptomatic CK elevation or any Grade CK elevation with symptoms or with renal impairment occurs, hold dose for up to 4 wk. If improved to Grade 0–1 resume at reduced dose. If not resolved within 4 wk, permanently discontinue binimetinib.