inhibitor and CYP3A4 substrate. (Minor) Use caution if coadministration of ribociclib with omeprazole is necessary, as the systemic exposure of omeprazole may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and omeprazole is a CYP3A4 substrate.
Anagrelide: (Major) Avoid coadministration of ribociclib with anagrelide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ventricular tachycardia and TdP have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Concomitant use may increase the risk for QT prolongation.
Apomorphine: (Major) Avoid coadministration of ribociclib with apomorphine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. However, concomitant use may increase the risk for QT prolongation.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of ribociclib, a moderate CYP3A4 inhibitor, with aprepitant/fosaprepitant, a CYP3A4 substrate, due to substantially increased exposure of aprepitant. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely. If coadministration cannot be avoided, use caution and monitor for an increase in treatment-related adverse effects (e.g., neutropenia, QT prolongation) for several days after administration of a multi-day aprepitant regimen. Increased ribociclib exposure may also occur with multi-day regimens of oral aprepitant, resulting in increased ribociclib-related adverse reactions, including QT prolongation. Ribociclib is a CYP3A4 substrate and aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Arformoterol: (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as arformoterol as compared to short-acting beta-agonists.
Aripiprazole: (Major) Avoid coadministration of ribociclib with aripiprazole due to an increased risk for QT prolongation. In addition, ribociclib is a moderate CYP3A4 inhibitor and aripiprazole is a partial CYP3A4 substrate. If aripiprazole and ribociclib are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. Because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based u |
