Drug Interaction Report

MONITOR: Coadministration with sarecycline may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) transporter. The proposed mechanism is decreased clearance in the intestine, kidney, and/or liver due to inhibition of P-gp-mediated efflux by sarecycline. When the probe P-gp substrate digoxin was coadministered with a single 150 mg dose of sarecycline, digoxin peak plasma concentration (Cmax) increased by 26%.

MANAGEMENT: Caution is advised when sarecycline is used concurrently with drugs that are P-gp substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever sarecycline is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of trametinib. In study subjects, administration of a single dose of trametinib with a high-fat, high-calorie meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 70% and 24%, respectively, and delayed Tmax by approximately 4 hours compared to administration in the fasted state.

MANAGEMENT: Trametinib should be taken at least 1 hour before or 2 hours after a meal.