ively metabolized by CYP3A4 and secobarbital is a CYP3A4 inducer.
Sertraline: (Major) Avoid coadministration of ribociclib with sertraline due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of sertraline 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. There have been postmarketing reports of QT prolongation and TdP during treatment with sertraline. Concomitant use may increase the risk for QT prolongation. Ribociclib is also a moderate CYP3A4 inhibitor and sertraline is a CYP3A4 substrate.
Sevoflurane: (Major) Avoid coadministration of ribociclib with halogenated anesthetics due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Halogenated anesthetics can also prolong the QT interval. Concomitant use may increase the risk for QT prolongation.
Short-acting beta-agonists: (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.
Sibutramine: (Moderate) Use caution if ribociclib is coadministered with sibutramine, as the systemic exposure of sibutramine may increase resulting in sibutramine-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and sibutramine is a CYP3A4 substrate.
Sildenafil: (Moderate) Use caution if coadministration of ribociclib with sildenafil is necessary, as the systemic exposure of sildenafil may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a CYP3A4 inhibitor and sildenafil is a CYP3A4 substrate. Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors.
Silodosin: (Moderate) Use caution if coadministration of ribociclib with silodosin is necessary, as the systemic exposure of silodosin may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and silodosin is a CYP3A4 substrate. The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been eva luated. However, administration with strong CYP3A4 inhibitors is contraindicated due to a significant increase in exposure to silodosin. Moderate 3A4 inhibitors may also increase the exposure to silodosin and should therefore be used with caution and close monitoring for adverse events.
Simeprevir: (Moderate) Use caution if coadministration of ribociclib with simeprevir is necessary, as the systemic exposure of simeprevir may be increased resulting in increase in treatment-related adverse reactions; adjust the dose of simeprevir if necessary. Exposure to ribociclib may also increase, increasing in ribociclib-related adverse reactions (e.g., neutropenia, QT prolongation). Both simeprevir and ribociclib are CYP3A4 substrates. Simeprevir is also a mild intestinal CYP3A4 inhibitor and ribociclib is a moderate CYP3A4 inhibit |
