ncomitant use may increase the risk for QT prolongation.
Lomitapide: (Severe) Concomitant use of ribociclib and lomitapide is contraindicated; if treatment with ribociclib is unavoidable, lomitapide should be stopped during treatment. Ribociclib is a moderate CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. While the concomitant use of moderate CYP3A4 inhibitors has not been studied, lomitapide exposure will likely increase significantly in the presence of these inhibitors; strong inhibitors of CYP3A4 increase lomitapide exposure approximately 27-fold.
Loperamide: (Major) Avoid coadministration of ribociclib with loperamide due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of loperamide may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and loperamide is a CYP3A4 substrate in vitro.
Loperamide; Simethicone: (Major) Avoid coadministration of ribociclib with loperamide due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of loperamide may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and loperamide is a CYP3A4 substrate in vitro.
Lopinavir; Ritonavir: (Severe) Coadministration of ribociclib with lopinavir is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to lopinavir may also increase. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Lopinavir has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and lopinavir is a strong CYP3A4 inhibitor; exposure to ribociclib may be increased. Additionally, ribociclib is a moderate CYP3A4 inhibitor and lopinavir is a CYP3A4 substrate. (Severe) Coadministration of ribociclib with ritonavir is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to ritonavir may also increase. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ritonavir has also been associated with QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and ritonavir is a strong CYP3A4 inhibitor; exposure to ribociclib may be increased. Coadministration with ritonavir, a strong CYP3A4 inhibitor increased the ribociclib AUC and Cmax by 3.2-fold and 1.7-fold, respectively, in healthy volunteers. Additionally, ribociclib is a moderate CYP3A4 inhibitor and ritonavir is a CYP3A4 substrate.
Loratadine: (Minor) Use caution if coadministration of ribociclib with loratadine is necessary, as the systemic exposure of loratadine may |
