educed by 150 mg.
ALT or AST elevation >3 times ULN with concurrent total bilirubin elevation >2 times ULN (in the absence of cholestasis or haemolysis)
Permanently discontinue Zykadia.
Any grade treatment-related interstitial lung disease (ILD)/pneumonitis
Permanently discontinue Zykadia.
QT corrected for heart rate (QTc) >500 msec on at least 2 separate electrocardiograms (ECGs)
Withhold Zykadia until recovery to baseline or to a QTc ≤480 msec, check and if necessary correct electrolytes, then reinitiate with dose reduced by 150 mg.
QTc >500 msec or >60 msec change from baseline and torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia
Permanently discontinue Zykadia.
Bradycardiaa (symptomatic, may be severe and medically significant, medical intervention indicated)
Withhold Zykadia until recovery to asymptomatic (grade ≤1) bradycardia or to a heart rate of 60 beats per minute (bpm) or above.
eva luate concomitant medicinal products known to cause bradycardia, as well as anti-hypertensive medicinal products.
If a contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, reinitiate Zykadia at the previous dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.
If no contributing concomitant medicinal product is identified, or if contributing concomitant medicinal products are not discontinued or dose modified, reinitiate Zykadia with dose reduced by 150 mg upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above.
Bradycardiaa (life-threatening consequences, urgent intervention indicated)
Permanently discontinue Zykadia if no contributing concomitant medicinal product is identified.
If a contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, reinitiate Zykadia with dose reduced by 150 mg upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, with frequent monitoringb.
Persistent hyperglycaemia greater than 250 mg/dl despite optimal anti-hyperglycaemic therapy
Withhold Zykadia until hyperglycaemia is adequately controlled, then reinitiate Zykadia with dose reduced by 150 mg.
If adequate glucose control cannot be achieved with optimal medical management, permanently discontinue Zykadia.
Lipase or amylase elevation grade ≥3
Withhold Zykadia until lipase or amylase returns to grade ≤1, then reinitiate with dose reduced by 150 mg.
a Heart rate less than 60 beats per minutes (bpm)
b Permanently discontinue in the event of recurrence
Strong CYP3A inhibitors
Avoid concomitant use of strong CYP3A inhibitors during treatment with Zykadia (see section 4.5). If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the dose by approximately one third (dose not clinically verified), rounded to the nearest multiple of the 150 mg dosage strength. Patients should be carefully monitored for safety.
If long-term concomitant treatment with a strong CYP3A inhibitor is necessary and the patient tolerates the reduced dose well, the dose may be increased again with careful monitoring for safety, to avoid potential under-treatment.
After discontinuation of a strong CYP3A inhibitor, resume at the dose that was taken prior to initiating the strong CYP3A inhibitor.
CYP3A substrates
When ceritinib is co-administered with oth |
