Ribociclib

Neutropenia commonly occurs, including grades 3 and 4 neutropenia. The median time to onset for grade 2 or higher neutropenia was 16 days. The median recovery for grade 3 or higher neutropenia was 15 days (resolution to normal levels or to less than grade 3 toxicity). Neutropenic fever has been observed. Monitor blood counts (baseline, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically necessary). Neutropenia may require treatment interruption, dose reduction and/or discontinuation (depending on the severity). Anemia, thrombocytopenia, and lymphopenia have also been observed.

ALT and/or AST elevations have been observed, including grade 3 or 4 events. The median time to onset for grade 3 or higher transaminase elevations was 57 days; the median time for grade 3 or higher elevations to resolve to grade 2 or lower was 24 days. Concurrent elevation of ALT or AST >3 times ULN and total bilirubin >2 times ULN (with normal alkaline phosphatase and in the absence of cholestasis) occurred (rare); all cases resolved following ribociclib discontinuation. Monitor liver function tests (baseline, every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles and as clinically necessary). Depending on the severity, hepatobiliary toxicity may require treatment interruption, dose reduction and/or discontinuation.

Ribociclib is associated with concentration-dependent QT prolongation, with an estimated mean increase in the QT interval exceeding 20 msec at the mean steady-state Cmax of a 600 mg once daily dose. QTcF interval prolongation >500 msec has been observed, as well as QTcF prolongations >60 msec from baseline. QT interval changes occurred within the initial 4 weeks of ribociclib therapy and were reversible with treatment interruption. Torsades de pointes has not been reported, although syncope occurred in a small percentage of patients. One sudden death was reported in a patient with grade 3 hypokalemia and grade 2 QT prolongation who was receiving ribociclib in combination with letrozole. Evaluate ECG prior to treatment initiation. Initiate treatment only in patients with QTcF Disease-related concerns:

Reduced initial doses are recommended for moderate to severe impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.