b is a moderate CYP3A4 inhibitor and midazolam is a CYP3A4 substrate. In a drug interaction study in healthy volunteers, the midazolam AUC (0-inf) and Cmax values were increased 3.8-fold and 2.1-fold, respectively, when midazolam was administered following 8 days of ribociclib 400 mg daily compared with midazolam administered alone.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and ribociclib; both drugs have been reported to increase the QT interval. If coadministration cannot be avoided, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Electrocardiogram changes occurred within the first 4 weeks of treatment and were reversible with dose interruption.
Mifepristone, RU-486: (Major) Avoid coadministration of ribociclib with mifepristone due to an increased risk for QT prolongation. Additionally, the systemic exposure of both drugs may be increased resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation). Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor. Mifepristone is a moderate CYP3A4 inhibitor and substrate.
Mirabegron: (Moderate) Use caution if coadministration of ribociclib with mirabegron is necessary, as the systemic exposure of mirabegron may be increased resulting in increase in treatment-related adverse reactions. Exposure to ribociclib may also increase, increasing in ribociclib-related adverse reactions (e.g., neutropenia, QT prolongation). Ribociclib is a moderate CYP3A4 inhibitor and mirabegron is a CYP3A4 substrate. Ribociclib is also extensively metabolized by CYP3A4 and mirabegron is a weak CYP3A4 inhibitor.
Mirtazapine: (Moderate) Use caution if coadministration of ribociclib with mirtazapine is necessary, as the systemic exposure of mirtazapine may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and mirtazapine is a CYP3A4 substrate.
Mitotane: (Major) Avoid coadministration of ribociclib with mitotane, as the systemic exposure of ribociclib may be decreased resulting in decreased efficacy; consider an alternative treatment with less potential to induce CYP3A. Ribociclib is extensively metabolized by CYP3A4 and mitotane is a strong CYP3A4 inducer.
Modafinil: (Moderate) Use caution if coadministration of ribociclib with modafinil is necessary, as the systemic exposure of modafinil may be increased resulting in an increase in treatment-related adverse reactions. Exposure to ribociclib may also decrease, resulting in decreased efficacy. Ribociclib is a CYP3A4 inhibitor and modafinil is a CYP3A4 substrate.
Moxifloxacin: (Major) Avoid coadministration of ribociclib with moxifloxacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxaci |
