• Assess for ILD/pneumonitis (dyspnea, cough, fever). If any Grade ILD/pneumonitis occurs, permanently discontinue ensartinib.
• Assess for dermatologic adverse reactions (DRESS, rash, pruritus, photosensitivity). If Grade 1 dermatologic reactions occur, consider topical corticosteroids. If Grade 2 dermatologic reactions occur, administer topical corticosteroids. If no improvement in ≤7 days after starting topical corticosteroids, administer PO corticosteroids. If no improvement in ≤7 days after starting PO corticosteroids, hold ensartinib until Grade ≤1. Resume at ↓ dose. If Grade 3 dermatologic reactions occur, hold ensartinib. Administer topical corticosteroids. If no improvement after 7 days of starting topical corticosteroids, administer PO corticosteroids. Resume at ↓ dose upon improvement to Grade ≤1. If Grade 4 dermatologic reactions occur, permanently discontinue ensartinib. Administer systemic corticosteroids and consider antibiotic use.
• Assess and monitor for bradycardia (HR <60 bpm) during treatment. If symptomatic bradycardia occurs, hold ensartinib until asymptomatic or resting HR >60 bpm. If a concurrent medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ensartinib at same dose when asymptomatic bradycardia or resting HR >60 bpm. If no concurrent medication known to cause bradycardia is identified or if contributing concurrent medications are not discontinued or dose adjusted, resume ensartinib at ↓ dose when asymptomatic or resting HR >60 bpm. If bradycardia with life-threatening consequences occurs or if urgent intervention indicated, permanently discontinue ensartinib if no contributing concurrent medication is identified. If contributing concurrent medication is identified and discontinued or dose adjusted, resume ensartinib at ↓ dose when asymptomatic bradycardia or a resting HR of >60 bpm, with frequent monitoring as clinically indicated. For recurrence, permanently discontinue ensartinib.
• Assess for visual disturbances (blurred vision, diplopia, photopsia, vitreous floaters, visual impairment, visual field defect, ↓ visual acuity). If Grade 2 or 3 visual disturbances occur, hold ensartinib until Grade ≤1; then resume at ↓ dose. If Grade 4 visual disturbances occur, permanently discontinue ensartinib. Obtain an ophthalmologic evaluation for patients with new or worsening visual symptoms.
• Assess for other adverse reactions. If Grade 3 or 4 adverse reactions occur, hold ensartinib until Grade ≤1. Resume at ↓ dose. If recurrent Grade 4 adverse reactions occur, permanently discontinue ensartinib.

Lab Test Considerations:

• Verify negative pregnancy status before starting treatment.
• Monitor fasting serum glucose at baseline and periodically during therapy. May cause hyperglycemia. If Grade 3 hyperglycemia (>250 mg/dL) despite antihyperglycemic therapy or Grade 4 hyperglycemia occurs, hold ensartinib until hyperglycemia controlled; then resume at ↓ dose. If hyperglycemic control cannot be achieved with medical management, permanently discontinue ensartinib.
• Monitor ALT, AST, and total bilirubin at baseline, then every 2 wk during 1st cycle, and then monthly and as clinically indicated. May cause hepatotoxicity. If Grade 3 or 4 ↑ (>5 times ULN) of either ALT or AST with concurrent total bilirubin ↑≤ 2 times ULN occurs, hold ensartinib until Grade ≤1 (≤3 times ULN). Resume at ↓ dose. If Grade 2–4 ↑ (>3 times ULN) of either ALT or AST with concurrent total bilirubin ↑ >2 times ULN in the absence of cholestasis or hemolysis occurs, permanently discontinue ensartinib.
• Monitor CK levels. If CK ↑ >5 times ULN, temporarily hold ensartinib until recovery to baseline or ≤2.5 times ULN; then resume at same dose. If CK ↑ >10 times ULN or 2nd occurrence of CK ↑ >5 times ULN, temporarily hold ensartinib until recovery to baseline or ≤2.5 times ULN; then resume at ↓ dose.
• Monitor uric acid level at baseline and periodically during therapy. May cause hyperuricemia. If symptomatic or Grade 4 hyperuricemia occurs, start urate-lowering medication. Hold ensartinib until improvement of signs/symptoms. Resume at same or ↓ dose.
• May ↓ albumin, phosphate, calcium, sodium, potassium, lymphocytes, and hemoglobin. May ↑ serum creatinine, magnesium, amylase, and gamma glutamyl transferase.