ntervals. Concomitant use may increase the risk for QT prolongation.
Dolutegravir: (Minor) Use caution if coadministration of ribociclib with dolutegravir is necessary, as the systemic exposure of dolutegravir may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a CYP3A4 inhibitor in vitro at clinically relevant concentrations. Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A.
Donepezil: (Major) Avoid coadministration of ribociclib with donepezil due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of donepezil 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. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and donepezil is a CYP3A4 substrate.
Donepezil; Memantine: (Major) Avoid coadministration of ribociclib with donepezil due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of donepezil 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. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and donepezil is a CYP3A4 substrate.
Doxepin: (Major) Avoid coadministration of ribociclib with doxepin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concomitant use may increase the risk for QT prolongation.
Doxorubicin: (Major) Avoid coadministration of ribociclib with doxorubicin due to an increased risk for QT prolongation. Systemic exposure of doxorubicin 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. Acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and doxorubicin is a CYP3A4 substrate.
Dronabinol, THC: (Moderate) Use caution if coadministration of ribociclib with dronabinol is necessary, as the systemic exposure of dronabinol may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor. Dronabinol is primarily metabolized by CYP2C9 and CYP3A4.
Dronedarone: (Severe) Because of the potential for torsade de pointes (TdP), use of ribociclib with dronedarone is contraindicated. Additionally, the systemic exposure of ribociclib may be |
