• Monitor ECG prior to starting therapy. Avoid administering ribociclib to patient with QT interval >450 msec. Repeat ECG on Day 14 of first cycle, beginning of 2nd cycle, and as indicated. If QT interval >480 msec, suspend therapy. If QT interval prolongation resolves to <481 msec, resume therapy at same dose level. If QT ≥481 msec recurs, interrupt dose until QT interval resolves to <481 msec; then resume ribociclib at next lower dose level. If QT interval >500 msec, withhold therapy if >500 msec on at least 2 separate ECGs (within same visit). If QT interval prolongation resolves to <481 msec, resume therapy at next lower dose. If QT interval prolongation is either >500 msec or >60 msec change from baseline AND associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, unexplained syncope, or signs and symptoms of serious arrhythmia, permanently discontinue ribociclib.
• Monitor for signs and symptoms of ILD/pneumonitis (hypoxia, cough, dyspnea) during therapy. If Grade 1 symptoms (asymptomatic) occur, continue dose and treat symptoms. If Grade 2 symptoms (symptomatic) occur, hold therapy until ≤Grade 1. Resume at next lower dose. If Grade 2 recurs, discontinue ribociclib permanently. If Grade 3 (severe symptomatic) or Grade 4 symptoms (life-threatening) occur, permanently discontinue therapy.
• Monitor for signs and symptoms of cutaneous reactions (rash, erythema, purpura) during therapy. If reactions are Grade 1 (< 10% body surface area [BSA] with active skin toxicity, no signs of systemic involvement) or Grade 2 (10–30% BSA with active skin toxicity, no signs of systemic involvement), continue at same dose and initiate medical therapy and monitor as clinically indicated. If Grade 3 reaction (severe rash not responsive to medical management; >30% BSA with active skin toxicity, signs of systemic involvement present; SJS) occurs, hold ribociclib until the cause of the reaction has been determined. If the cause is SJS, TEN, or DRESS, permanently discontinue therapy. If cause is not SJS, TEN, DRESS, hold dose until recovery to Grade ≤ 1, then resume ribociclib at same dose level. If the cutaneous adverse reaction still recurs at Grade 3, resume ribociclib at the next lower dose level. If Grade 4 reaction (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences; TEN) occurs, permanently discontinue ribociclib.

Lab Test Considerations:

• Verify negative pregnancy test prior to starting therapy.
  • Monitor serum electrolytes (potassium, calcium, phosphorous, magnesium) prior to starting therapy, at beginning of first 6 cycles, and as indicated. Correct abnormalities before starting therapy.
  • Monitor liver function before starting therapy, every 2 wk for first 2 cycles, at beginning of each subsequent 4 cycles, and as indicated. For AST and/or ALT ↑ from baseline, WITHOUT ↑ total bilirubin >2 × upper limit of normal (ULN): Grade 1 (>ULN to 3 × ULN), No dose adjustment. Grade 2 (>3 to 5 × ULN), Baseline at <Grade 2: Hold dose until recovery to ≤baseline grade, then resume at same dose. If Grade 2 recurs, resume ribociclib at next lower dose. Do not interrupt dose for Grade 2 at baseline. Grade 3 (>5 to 20 × ULN), withhold dose until recovery to ≤baseline grade, then resume at next lower dose. If Grade 3 recurs, discontinue ribociclib. Grade 4 (>20 × ULN), discontinue ribociclib. Combined ↑ in AST and/or ALT WITH total bilirubin ↑, in absence of cholestasis: If ALT and/or AST >3 × ULN along with total bilirubin >2 × ULN irrespective of baseline grade, discontinue ribociclib.
  • Monitor CBC before starting therapy, every 2 wk for first 2 cycles, at beginning of each subsequent 4 cycles, and as indicated. If Grade 1 or 2 (ANC 1000/mm³ to <lower limit of normal) occurs, no dose adjustment required. If Grade 3 (ANC 500–1000/mm³) occurs, interrupt dose until recovery to Grade ≤2. Resume therapy at same dose. If toxicity recurs at Grade 3, hold dose until recovery, then resume ribociclib at next lower dose. If Grade 3 febrile neutropenia occurs, suspend therapy until recovery of neutropenia to Grade ≤2. Resume therapy at next lower dose. If Grade 4 (ANC <500/mm³) occurs, withhold therapy until recovery to Grade ≤2. Resume ribociclib at next lower dose.