reased 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.
Metformin; Repaglinide: (Moderate) Use caution if coadministration of ribociclib with repaglinide is necessary, as the systemic exposure of repaglinide may be increased resulting in increase in treatment-related adverse reactions including hypoglycemia; adjust the dose of repaglinide if necessary. Ribociclib is a moderate CYP3A4 inhibitor and repaglinide is a CYP3A4 substrate.
Metformin; Saxagliptin: (Moderate) Use caution if coadministration of ribociclib with saxagliptin is necessary, as the systemic exposure of saxagliptin may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and saxagliptin is a CYP3A4 substrate.
Methadone: (Major) Avoid coadministration of ribociclib with methadone due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of methadone may also be increased resulting in an increase in methadone-related adverse reactions including respiratory depression and sedation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Methadone has also been associated with an increased risk of QT prolongation and TdP, especially at higher doses (> 200 mg per day but averaging approximately 400 mg per day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and methadone is a CYP3A4 substrate.
Methohexital: (Moderate) Use caution if coadministration of ribociclib with methohexital is necessary, as the systemic exposure of ribociclib may be decreased resulting in decreased efficacy. Ribociclib is extensively metabolized by CYP3A4 and methohexital is a CYP3A4 inducer.
Methylprednisolone: (Moderate) Use caution if coadministration of ribociclib with methylprednisolone is necessary, as the systemic exposure of methylprednisolone may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and methylprednisolone is a CYP3A4 substrate.
Metronidazole: (Major) Avoid coadministration of ribociclib with metronidazole due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Potential QT prolongation has been reported in limited case reports with metronidazole. Concomitant use may increase the risk for QT prolongation.
Metyrapone: (Moderate) Use caution if coadministration of ribociclib with metyrapone is necessary, as the systemic exposure of ribociclib may be decreased resulting in decreased efficacy. Ribociclib is extensively metabolized by CYP3A4 and metyrapone is a CYP3A4 inducer.
Midazolam: (Moderate) Use caution if coadministration of ribociclib with midazolam is necessary, as the systemic exposure of midazolam was significantly increased in a drug interaction study. Adjust the dose of midazolam if necessary. Ribocicli |
