xtensively metabolized by CYP3A4 and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased the ribociclib AUC and Cmax by 89% and 81%, respectively, in healthy volunteers.
Gefitinib: (Moderate) Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and ribociclib are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and ribociclib is a moderate CYP3A4 inhibitor; coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations.
Gemifloxacin: (Major) Avoid coadministration of ribociclib with gemifloxacin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin; the likelihood of QTc prolongation may increase with increasing dose of the drug. Concomitant use may increase the risk for QT prolongation.
Glimepiride; Pioglitazone: (Moderate) Coadminister ribociclib and pioglitazone with caution, as the systemic exposure of pioglitazone may be increased resulting in pioglitazone-related adverse reactions; adjust the dose of pioglitazone if necessary. Exposure to ribociclib may also decrease, resulting in reduced efficacy. Ribociclib is extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor in vitro; pioglitazone is a CYP3A4 substrate and inducer.
Glycopyrrolate; Formoterol: (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 formoterol as compared to short-acting beta-agonists.
Goserelin: (Major) Avoid coadministration of ribociclib with goserelin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
Granisetron: (Major) Avoid coadministration of ribociclib with granisetron due to an increased risk for QT prolongation. Systemic exposure of granisetron 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. Granisetron has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and granisetron is a CYP3A4 substrate.
Grapefruit juice: (Major) Avoid the concomitant use of ribociclib and grapefruit or grapefruit juice or pomegranate or pomegranate juice; the systemic exposure of ribociclib may be increased resulting in an increase in ribociclib-related adverse reactions. Ribociclib is a CYP3A4 substrate; grapefruit and pomegranates are strong CYP3A inhibitors. Coadministration with another strong CYP3A4 inhibitor increased the ribociclib AUC and Cmax values by 3.2-fold a |
