or QT prolongation. Systemic exposure of clomipramine 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. 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. Ribociclib is also a moderate CYP3A4 inhibitor and clomipramine is a CYP3A4 substrate.
Clonazepam: (Moderate) Use caution if coadministration of ribociclib with clonazepam is necessary, as the systemic exposure of clonazepam may be increased resulting in increase in treatment-related adverse reactions including sedation and respiratory depression; adjust the dose of clonazepam if necessary. Ribociclib is a moderate CYP3A4 inhibitor and clonazepam is a CYP3A4 substrate.
Clopidogrel: (Minor) Use caution if coadministration of ribociclib with clopidogrel is necessary, as the efficacy of clopidogrel may be decreased. Ribociclib is a moderate CYP3A4 inhibitor. Clopidogrel requires hepatic biotransformation to an active metabolite; this activation is mediated primarily by CYP2C19 and to a lesser extent by CYP3A, CYP2B6, and CYP1A2. Concomitant use may decrease exposure of the active metabolite.
Clorazepate: (Moderate) Use caution if coadministration of ribociclib with clorazepate is necessary, as the systemic exposure of the active metabolite of clorazepate may be increased resulting in an increase in treatment-related adverse reactions; adjust the dose of clorazepate if necessary. Ribociclib is a moderate CYP3A4 inhibitor. Clorazepate is a pro-drug converted to N-desmethyldiazepam in the GI tract; N-desmethyldiazepam is metabolized by 2C19 and 3A4.
Clozapine: (Major) Avoid coadministration of ribociclib with clozapine due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of clozapine may also be increased resulting in an increase in clozapine-related adverse reactions. Consider a dose reduction of clozapine if necessary. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Treatment with clozapine has also been associated with QT prolongation, TdP, cardiac arrest, and sudden death. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and clozapine is a CYP3A4 substrate.
Cobicistat: (Severe) Coadministration of ribociclib with cobicistat is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to cobicistat may also increase. Ribociclib is extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor; cobicistat is a moderate CYP3A4 inhibitor and CYP3A4 substrate.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Severe) Coadministration of ribociclib with cobicistat is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to cobicistat may also increase. Ribociclib is extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor; cobicistat is a moderate CYP3A4 inhibitor and CYP3A4 substrate.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Severe) Coadministration of ribocicli |
