b 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.
Cobimetinib: (Major) Avoid coadministration of ribociclib with cobimetinib, as the systemic exposure of cobimetinib may be increased resulting in an increase in treatment-related adverse reactions. Ribociclib is a CYP3A4 inhibitor in vitro at clinically relevant concentrations and cobimetinib is a CYP3A4 substrate in vitro.
Codeine: (Moderate) Use caution if coadministration of ribociclib with codeine is necessary, as the systemic exposure of codeine may be increased resulting in an increase in treatment-related adverse reactions including sedation and respiratory depression; adjust the dose of codeine if necessary. Ribociclib is a moderate CYP3A4 inhibitor. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norocodeine; norcodeine does not have analgesic properties. Concomitant use may result in an increase in codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and increased morphine concentrations.
Codeine; Guaifenesin: (Moderate) Use caution if coadministration of ribociclib with codeine is necessary, as the systemic exposure of codeine may be increased resulting in an increase in treatment-related adverse reactions including sedation and respiratory depression; adjust the dose of codeine if necessary. Ribociclib is a moderate CYP3A4 inhibitor. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norocodeine; norcodeine does not have analgesic properties. Concomitant use may result in an increase in codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and increased morphine concentrations.
Codeine; Phenylephrine; Promethazine: (Major) Avoid coadministration of ribociclib with promethazine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Concomitant use may increase the risk for QT prolongation. (Moderate) Use caution if coadministration of ribociclib with codeine is necessary, as the systemic exposure of codeine may be increased resulting in an increase in treatment-related adverse reactions including sedation and respiratory depression; adjust the dose of codeine if necessary. Ribociclib is a moderate CYP3A4 inhibitor. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norocodeine; norcodeine does not have analgesic properties. Concomitant use may result in an increase in codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and increased morphine concentrations.
Codeine; Promethazine: (Major) Avoid coadministration of ribociclib with promethazine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Concomitant use may increase the risk for QT prolongation. (Moderate) Use caution if coadministration of ribociclib with codeine is necessary, as the systemic exposure of codeine may be increased resulting in an increase in treatment-re |
