ALT or AST elevation of Grade 3 (> 5 times Temporarily withhold until recovery to ≥ ULN) with total bilirubin 2 times ULN baseline or Grade 1 ( 3 times ULN), then resume at reduced dose (see Table 6). ALT or AST elevation of 2 (> 3 times Permanently discontinue ALECENSA. ≥ ULN) with total bilirubin elevation > 2 times ULN in the absence of cholestasis or haemolysis Bradycardiaa Grade 2 or Grade 3 Temporarily withhold until recovery to Grade ≤ (symptomatic, may be severe and medically 1 (asymptomatic) bradycardia or to a heart rate significant, medical intervention indicated) of 60 bpm. Evaluate concomitant ≥ medications known to cause bradycardia, as well as anti-hypertensive medications. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume at previous dose upon recovery to Grade 1 (asymptomatic) ≤ bradycardia or to a heart rate of 60 bpm. ≥ If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume at reduced dose (see 6) upon recovery to Grade 1 (asymptomatic) ≤ bradycardia or to a heart rate of 60 bpm. ≥ Bradycardiaa Grade 4 (life-threatening Permanently discontinue if no contributing consequences, urgent intervention indicated) concomitant medication is identified. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume at reduced dose (see Table 6) upon recovery to Grade 1 (asymptomatic) ≤ bradycardia or to a heart rate of 60 bpm, with ≥ frequent monitoring as clinically indicated. Permanently discontinue in case of recurrence. CPK elevation > 5 ULN Temporarily withhold until recovery to baseline or to 2.5 times ULN, then resume at ≤ same dose.
ALT or AST elevation of Grade ≥ 3 (> 5 times ULN) with total bilirubin 2 times ULN Temporarily withhold until recovery to baseline or Grade 1 ( 3 times ULN), then resume at reduced dose (see Table 6). ALT or AST elevation of ≥ 2 (> 3 times ULN) with total bilirubin elevation > 2 times ULN in the absence of cholestasis or haemolysis Permanently discontinue ALECENSA. Bradycardiaa Grade 2 or Grade 3 (symptomatic, may be severe and medically significant, medical intervention indicated) Temporarily withhold until recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm. Evaluate concomitant medications known to cause bradycardia, as well as anti-hypertensive medications. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume at previous dose upon recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume at reduced dose (see 6) upon recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm. Bradycardiaa Grade 4 (life-threatening consequences, urgent intervention indicated) Permanently discontinue if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume at reduced dose (see Table 6) upon recovery to ≤ Grade 1 (asymptomatic) bradycardia or to a heart rate of ≥ 60 bpm, with frequent monitoring as clinically indicated. Permanently discontinue in case of recurrence. CPK elevation > 5 ULN Temporarily withhold until recovery to baseline or to ≤ 2.5 times ULN, then resume at same dose.