Severe) Because of the potential for torsade de pointes (TdP), use of ribociclib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Additionally, ribociclib is a moderate CYP3A4 inhibitor. Pimozide is partially metabolized by CYP3A4, and has a narrow therapeutic window; coadministration may increase systemic exposure to pimozide.
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.
Pirbuterol: (Minor) Coadministration may result in additive effects on the QT interval. 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 such as ribociclib. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
Posaconazole: (Severe) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are CYP3A4 substrates, such as ribociclib, is contraindicated. Posaconazole has been associated with QT prolongation and torsade de pointes. Additionally, ribociclib is extensively metabolized by CYP3A4 and posaconazole is a strong CYP3A4 inhibitor.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone, dehydroepiandrosterone, DHEA is converted via hydrosteroid dehydrogenases and aromatase into androstenedione, testosterone, and estradiol by peripheral tissues. Prasterone or DHEA supplements should not be given concurrently with any aromatase inhibitors, as DHEA could interfere with the pharmacologic action of the aromatase inhibitor and compromise aromatase inhibitor effectiveness. Conversely, aromatase inhibitors (e.g., aminoglutethimide, anastrozole, exemestane, letrozole, testolactone, vorozole) could interfere with biotransformation of DHEA.
Prednisolone: (Moderate) Use caution if coadministration of ribociclib with prednisolone is necessary, as the systemic exposure of prednisolone may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and prednisolone is a CYP3A4 substrate.
Prednisone: (Moderate) Use caution if coadministration of ribociclib with prednisone is |
