tion, myocardial infarction, QT prolongation, thyroid disease
Avoid the use of ribociclib; letrozole in patients with long QT syndrome, uncontrolled or significant cardiac disease including cardiac arrhythmias, recent myocardial infarction, congestive heart failure, unstable angina and bradycardia or bradyarrhythmias, electrolyte imbalance (hypomagnesemia, hypokalemia, hypocalcemia), or in patients receiving medications known to prolong the QT interval or strongly inhibit CYP3A4 as this may lead to prolongation of the QTcF interval. Use ribociclib; letrozole with caution in patients with other conditions that may increase the risk of QT prolongation including hypertension, coronary artery disease, or in patients receiving medications known to cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation. Assess ECG prior to starting therapy; do not initiate treatment in patients with a QTcF greater than 450 msec. Repeat ECG at approximately day 14 of the first cycle, at the beginning of the second cycle, and then as clinically indicated. Prolongation of the QTcF interval may require interruption of therapy, dose reduction, or discontinuation of therapy; more frequent ECG monitoring is recommended if QT prolongation occurs. Monitor serum electrolytes (including potassium, calcium, phosphorous, and magnesium) prior to beginning therapy with ribociclib; letrozole, at the beginning of the first 6 cycles, and as clinically indicated; correct any electrolyte imbalance before starting therapy. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner, with estimated mean increase in QTc interval of 22.9 msec at the mean steady-state Cmax following administration at 600 mg once daily dose. These ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption; there are no reported cases of Torsades de Pointes (TdP).
Bone marrow suppression, neutropenia
Bone marrow suppression is commonly reported with ribociclib plus letrozole therapy, with neutropenia being the most frequently reported adverse reaction. The median time to onset of grade 2 or higher neutropenia was 16 days, with the median time to resolution (to normalization or less than grade 3) of 15 days. Monitor a complete blood count (CBC) prior to initiating therapy with ribociclib, every 2 weeks for the first 2 cycles, prior to the next 4 cycles, and then as clinically indicated. A dose interruption, reduction, or discontinuation of therapy may be necessary for patients with an absolute neutrophil count (ANC) less than 1,000 cells/mm3.
Hepatic disease
Use ribociclib with caution in patients with baseline hepatic disease; a dose reduction is necessary in patients with baseline Child-Pugh class B or C hepatic disease. Hepatotoxicity, including elevated transaminases with or without an elevation in total bilirubin, has been reported in patients receiving therapy with ribociclib plus letrozole. The median time to onset of grade 3 or higher transaminase elevations was 57 days, with a median time to resolution to grade 2 or less of 24 days. Monitor liver function tests prior to initiating therapy with ribociclib, every 2 weeks for the first 2 cycles, prior to the next 4 cycles, and then as clinically indicated. A dose interruption, reduction, or discontinuation of therapy may be necessary. |
