• Assess for palmar-plantar erythrodysesthesia syndrome (palmar-plantar swelling, color changes, blisters, pain to touch). If Grade 2 palmar-plantar erythrodysesthesia syndrome occurs, hold ripretinib until Grade ≤1. If recovered in 7 days, resume at same dose; otherwise, if >7 days or symptoms recur, resume at ↓ dose and consider titrating up if Grade 1 or baseline maintained ≥28 days. If Grade 3 palmar-plantar erythrodysesthesia syndrome occurs, hold ripretinib ≥7 days or until Grade ≤1 or (max = 28 days). Resume at ↓ dose and consider titrating up if Grade ≤1 maintained ≥28 days.
• Perform dermatologic evaluation upon ripretinib initiation and routinely during therapy. If skin lesions occur, refer for dermatologic evaluation.
• Assess BP at baseline and as clinically indicated during therapy. Control hypertension prior to ripretinib initiation. If Grade 3 hypertension occurs, hold ripretinib until asymptomatic and BP controlled to Grade ≤1; then resume at same dose. If Grade 3 recurs, resume at ↓ dose. If Grade 4 hypertension occurs, permanently discontinue ripretinib.
• Monitor for cardiac dysfunction; assess LVEF with echocardiogram or MUGA scan at baseline and as clinically indicated. If Grade 3 or 4 left ventricular dysfunction occurs, permanently discontinue ripretinib.
• Assess surgical and other significant wounds for adequate healing during therapy with ripretinib.
• Monitor for arthralgias or myalgias. If Grade 2 arthralgias/myalgias occur, hold ripretinib until Grade ≤1. If recovered in 7 days, resume at same dose; otherwise, if >7 days or symptoms recur, resume at ↓ dose and consider titrating up if Grade ≤1 maintained ≥28 days. If Grade 3 arthralgias/myalgias occur, hold ripretinib for ≥7 days or until Grade ≤1 (max = 28 days). Resume at ↓ dose and consider titrating up if Grade ≤1 maintained ≥28 days.

Lab Test Considerations:

• Verify a negative pregnancy test before starting therapy.
• May ↑ lipase and ↓ phosphate.