Drug Interactions between Ambien and letrozole / ribociclib

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of zolpidem, which is partially metabolized by the isoenzyme. When a single 5 mg dose of zolpidem was administered to 12 healthy study subjects following treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 2 days), zolpidem peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 35% and 67%, respectively. Increased sedation and other pharmacodynamic effects were noted.

MANAGEMENT: Caution is advised when zolpidem is used with CYP450 3A4 inhibitors. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them, and to notify their physician if they experience excessive somnolence or dizziness.

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to ribociclib-mediated inhibition of CYP450 3A4 metabolism. In healthy study subjects, administration of midazolam, a sensitive CYP450 3A4 substrate, with multiple 400 mg daily doses of ribociclib increased the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.1-fold and 3.8-fold, respectively, compared to midazolam administered alone. When given at a clinically relevant dose of 600 mg daily, ribociclib is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold, respectively.

MANAGEMENT: Caution is advised when ribociclib is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.