n. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Concomitant use may increase the risk for QT prolongation.
Nafcillin: (Moderate) Use caution if coadministration of ribociclib with nafcillin is necessary, as the systemic exposure of ribociclib may be decreased resulting in decreased efficacy. Ribociclib is extensively metabolized by CYP3A4 and nafcillin is a moderate CYP3A4 inducer.
Nefazodone: (Major) Avoid coadministration of ribociclib with nefazodone, as the systemic exposure of both drugs may be increased resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation); consider an alternative treatment with less potential for CYP3A inhibition. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg once daily; if nefazodone is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of nefazodone. Ribociclib is extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor; nefazodone is a strong CYP3A4 inhibitor and CYP3A4 substrate.
Nelfinavir: (Severe) Coadministration of ribociclib with nelfinavir is contraindicated, as elevated plasma concentrations of ribociclib may be associated with QT prolongation; exposure to nelfinavir may also increase. Ribociclib is extensively metabolized by CYP3A4 and nelfinavir is a strong CYP3A4 inhibitor. Additionally, ribociclib is a moderate CYP3A4 inhibitor and nelfinavir is a CYP3A4 substrate.
Neratinib: (Major) Avoid concomitant use of ribociclib with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and ribociclib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
Netupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as ribociclib. The plasma concentrations of ribociclib can increase when co-administered with netupitant; the inhibitory effect on CYP3A4 can last for multiple days.
Nevirapine: (Moderate) Use caution if ribociclib is coadministered with nevirapine, as the systemic exposure of nevirapine may increase resulting in nevirapine-related adverse reactions. Exposure to ribociclib may also decrease, resulting in reduced efficacy. Ribociclib is extensively metabolized by CYP3A4 and is a moderate CYP3A4 inhibitor; nevirapine is both a CYP3A4 substrate and moderate inducer.
Niacin; Simvastatin: (Moderate) Use caution if ribociclib is coadministered with simvastatin, as the systemic exposure of simvastatin may increase resulting in simvastatin-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and simvastatin is a CYP3A4 substrate.
Nicardipine: (Moderate) Use caution if coadministration of ribociclib with nicardipine is necessary, as the systemic exposure of ribociclib may be increased resulting in an increase in ribociclib |
